Research on Innate Immunity and Inflammation

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Innate and Adaptive Immunity in Vaccination".

Deadline for manuscript submissions: closed (30 April 2020) | Viewed by 52786

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Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain
Interests: hepatitis C; molecular virology; innate immunity; virus-host interaction; antibody; inflammation; immunopathology; vaccine
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III (Campus Majadahonda), Madrid, Spain
Interests: HIV; hepatitis C; infectious diseases; immunology; virology; genetics; epidemiology; cirrhosis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Innate immunity and inflammation are closely interrelated and constitute an exciting field of intense investigation in multiple disciplines. Invading pathogens are detected by the host pattern recognition receptors (PRRs), which trigger intracellular immune signaling pathways to promote inflammation. This innate response is crucial to clear the infection and controlling adaptive immunity. Inflammation, however, has to be strictly controlled to avoid excessive host damage. Thus, the immune signaling pathways are tightly regulated to ensure a balanced inflammatory response. Therefore, we would like to encourage the presentation to this special issue recent advances in the understanding of the mechanisms of pathogen recognition by PRRs and their regulation (including post-translational modifications), as well as in the escape mechanisms and countermeasures developed by microbes and host, respectively. Identification of surrogate biomarkers defining early signatures of vaccine-induced inflammation may help to select safe candidate vaccines. Articles on this topic will also be welcome. Adding new information on these subjects may lead to a better understanding of the pathogenesis of different diseases and aid in the design of new therapeutic and prophylactic strategies.

Dr. Isidoro Martínez
Dr. Salvador Resino
Guest Editors

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Keywords

  • Innate Immunity
  • Inflammation
  • pattern recognition receptors
  • immune signaling pathways
  • vaccines

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Published Papers (14 papers)

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20 pages, 3271 KiB  
Article
Dendritic Cells and Myeloid Derived Suppressor Cells Fully Responsive to Stimulation via Toll-Like Receptor 4 Are Rapidly Induced from Bone-Marrow Cells by Granulocyte-Macrophage Colony-Stimulating Factor
by Ying Ying Kong, Kirsty Wilson, Vasso Apostolopoulos and Magdalena Plebanski
Vaccines 2020, 8(3), 522; https://doi.org/10.3390/vaccines8030522 - 12 Sep 2020
Cited by 11 | Viewed by 3727
Abstract
Dendritic cells (DCs) are commonly generated from bone marrow (BM) progenitor cells with granulocyte-macrophage colony-stimulating factor (GM-CSF) alone or in combination with interleukin 4 (IL-4). These cells are often harvested post day 5, when they acquire maturation markers and can stimulate T cells. [...] Read more.
Dendritic cells (DCs) are commonly generated from bone marrow (BM) progenitor cells with granulocyte-macrophage colony-stimulating factor (GM-CSF) alone or in combination with interleukin 4 (IL-4). These cells are often harvested post day 5, when they acquire maturation markers and can stimulate T cells. Apart from DCs, myeloid derived suppressor cells (MDSCs) are also found within these cultures. However, little is known about the functional characteristics of DCs and MDSCs before day 5. Herein, using a murine model, it is shown that early DCs and MDSCs, even in cultures with GM-CSF alone, upregulate fully maturation and activation surface molecules in response to the toll-like receptor 4 (TLR4) ligand lipopolysaccharide (LPS) stimulation. Despite initially displaying lower marker expression levels, these cells efficiently induced T cell stimulation and cytokine production. Interestingly, Gr-1int MDSCs increased their T cell co-stimulatory activity upon TLR4 stimulation. Additionally, early DCs and MDSCs exhibited differential endocytic capacity for viral sized nanoparticles and bacterial sized microparticles. DCs internalized both particle sizes, whilst MDSCs only internalized the larger microparticles, with reduced endocytic activity over time in the culture. These findings have unveiled an important role for the rapid initiation of productive immunity by GM-CSF, with promising implications for future vaccine and DC immunotherapy developments. Full article
(This article belongs to the Special Issue Research on Innate Immunity and Inflammation)
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16 pages, 703 KiB  
Article
Sex-Differential Impact of Human Cytomegalovirus Infection on In Vitro Reactivity to Toll-Like Receptor 2, 4 and 7/8 Stimulation in Gambian Infants
by Momodou Cox, Jane U. Adetifa, Fatou Noho-Konteh, Lady C. Sanyang, Abdoulie Drammeh, Magdalena Plebanski, Hilton C. Whittle, Sarah L. Rowland-Jones, Iain Robertson and Katie L. Flanagan
Vaccines 2020, 8(3), 407; https://doi.org/10.3390/vaccines8030407 - 22 Jul 2020
Cited by 1 | Viewed by 2541
Abstract
Human cytomegalovirus (HCMV) infection rates approach 100% by the first year of life in low-income countries. It is not known if this drives changes to innate immunity in early life and thereby altered immune reactivity to infections and vaccines. Given the panoply of [...] Read more.
Human cytomegalovirus (HCMV) infection rates approach 100% by the first year of life in low-income countries. It is not known if this drives changes to innate immunity in early life and thereby altered immune reactivity to infections and vaccines. Given the panoply of sex differences in immunity, it is feasible that any immunological effects of HCMV would differ in males and females. We analysed ex vivo innate cytokine responses to a panel of toll-like receptor (TLR) ligands in 108 nine-month-old Gambian males and females participating in a vaccine trial. We found evidence that HCMV suppressed reactivity to TLR2 and TLR7/8 stimulation in females but not males. This is likely to contribute to sex differences in responses to infections and vaccines in early life and has implications for the development of TLR ligands as vaccine adjuvants. Development of an effective HCMV vaccine would be able to circumvent some of these potentially negative effects of HCMV infection in childhood. Full article
(This article belongs to the Special Issue Research on Innate Immunity and Inflammation)
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14 pages, 5253 KiB  
Article
Liver Stiffness Hinders Normalization of Systemic Inflammation and Endothelial Activation after Hepatitis C Virus (HCV) Eradication in HIV/HCV Coinfected Patients
by Beatriz Álvarez, Clara Restrepo, Marcial García, María A. Navarrete-Muñoz, María A. Jiménez-Sousa, Laura Prieto, Alfonso Cabello, Sara Nistal, Salvador Resino, Miguel Górgolas, Norma Rallón and José M. Benito
Vaccines 2020, 8(2), 323; https://doi.org/10.3390/vaccines8020323 - 19 Jun 2020
Cited by 6 | Viewed by 3032
Abstract
Systemic inflammation, endothelial dysfunction and coagulopathy are of high clinical relevance in the management of people living with HIV (PLWH), and even more in patients coinfected with hepatitis C virus (HCV). It has been suggested a significant impact of HCV coinfection on these [...] Read more.
Systemic inflammation, endothelial dysfunction and coagulopathy are of high clinical relevance in the management of people living with HIV (PLWH), and even more in patients coinfected with hepatitis C virus (HCV). It has been suggested a significant impact of HCV coinfection on these conditions. However, HCV can be eradicated in most patients with the new direct-acting antivirals (DAAs) therapy. We have analyzed the effect of HCV on systemic inflammation, endothelial activation and coagulopathy in PLWH and its evolution after HCV eradication with DAAs. Twenty-five HIV/HCV coinfected (HIV/HCV group), 25 HIV monoinfected (HIV group) and 20 healthy controls (HC) were included in the study. All patients were on ART and HIV suppressed. Levels of fourteen markers of systemic inflammation, endothelial activation and coagulopathy (IL-1ß, IL-6, IL-12p70, IL-8, TNFα, D-dimer, Eotaxin, IL-18, IP-10, monocyte chemotactic protein-1 (MCP-1), plasminogen activator inhibitor-1 (PAI-1), TNFα receptor 1 (TNFR1), vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1)) were measured on plasma at baseline and after DAAs-mediated HCV eradication. Non-parametric tests were used to establish inter/intra-group differences. At baseline, the HIV/HCV group showed increased levels of IL-18 (p = 0.028), IP-10 (p < 0.0001), VCAM-1 (p < 0.0001) and ICAM-1 (p = 0.045), compared to the HC and HIV groups, with the highest levels for IL18 and IP10 observed in HIV/HCV patients with increased liver stiffness (≥7.1 KPa). Eradication of HCV with DAAs-based therapy restored some but not all the evaluated parameters. VCAM-1 remained significantly increased compared to HC (p = 0.001), regardless of the level of basal liver stiffness in the HIV/HCV group, and IP-10 remained significantly increased only in the HIV/HCV group, with increased level of basal liver stiffness compared to the HC and to the HIV groups (p = 0.006 and p = 0.049, respectively). These data indicate that DAAs therapy in HIV/HCV co-infected patients and HCV eradication does not always lead to the normalization of systemic inflammation and endothelial dysfunction conditions, especially in cases with increased liver stiffness. Full article
(This article belongs to the Special Issue Research on Innate Immunity and Inflammation)
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26 pages, 5576 KiB  
Article
Innate Lymphocyte Th1 and Th17 Responses in Elderly Hospitalised Patients with Infection and Sepsis
by John Davis Coakley, Eamon P. Breen, Ana Moreno-Olivera, Alhanouf I. Al-Harbi, Ashanty M. Melo, Brian O’Connell, Ross McManus, Derek G. Doherty and Thomas Ryan
Vaccines 2020, 8(2), 311; https://doi.org/10.3390/vaccines8020311 - 17 Jun 2020
Cited by 7 | Viewed by 3692
Abstract
Background: the role of innate immunity in human sepsis must be fully clarified to identify potential avenues for novel immune adjuvant sepsis therapies. Methods: A prospective observational study was performed including patients with sepsis (septic group), infection without sepsis (infection group), and healthy [...] Read more.
Background: the role of innate immunity in human sepsis must be fully clarified to identify potential avenues for novel immune adjuvant sepsis therapies. Methods: A prospective observational study was performed including patients with sepsis (septic group), infection without sepsis (infection group), and healthy controls (control group) in the setting of acute medical wards and intensive care units in a 1000-bed university hospital. A total of 42 patients with sepsis, 30 patients with infection, and 30 healthy controls were studied. The differentiation states of circulating mucosal associated invariant T (MAIT) cells and Natural Killer T (NKT) cells were characterised as naive (CD45RA+, CD197+), central memory (CD45RA, CD197+), effector memory (CD45RA, CD197), or terminally differentiated (CD45RA+, CD197). The differentiation states of circulating gamma-delta T lymphocytes were characterised as naive (CD45RA+, CD27+), central memory (CD45RA, CD27+), effector memory (CD45RA, CD27), or terminally differentiated (CD45RA+, CD27). The expression of IL-12 and IL-23 receptors, the transcription factors T-Bet and RORγt, and interferon-γ and IL-17a were analysed. Results: MAIT cell counts were lower in the septic group (p = 0.002) and the infection group (p < 0.001) than in the control group. The MAIT cell T-Bet expression in the infection group was greater than in the septic group (p = 0.012). The MAIT RORγt expression in the septic group was lower than in the control group (p = 0.003). The NK cell counts differed in the three groups (p < 0.001), with lower Natural Killer (NK) cell counts in the septic group (p < 0.001) and in the infection group (p = 0.001) than in the control group. The NK cell counts increased in the septic group in the 3 weeks following the onset of sepsis (p = 0.028). In lymphocyte stimulation experiments, fewer NK cells expressed T-Bet in the septic group than in the infection group (p = 0.002), and fewer NK cells expressed IFN-γ in the septic group than in the control group (p = 0.002). The NKT cell counts were lower in the septic group than both the control group (p = 0.05) and the infection group (p = 0.04). Fewer NKT cells expressed T-Bet in the septic group than in the infection group (p = 0.004). Fewer NKT cells expressed RORγt in the septic group than in the control group (p = 0.003). Fewer NKT cells expressed IFN-γ in the septic group than in both the control group (p = 0.002) and the infection group (p = 0.036). Conclusion: The clinical presentation of infection and or sepsis in patients is linked with a mosaic of changes in the innate lymphocyte Th1 and Th17 phenotypes. The manipulation of the innate lymphocyte phenotype offers a potential avenue for immune modulation in patients with sepsis. Full article
(This article belongs to the Special Issue Research on Innate Immunity and Inflammation)
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17 pages, 3370 KiB  
Article
Impact of Key Nicotinic AChR Subunits on Post-Stroke Pneumococcal Pneumonia
by Sandra Jagdmann, Claudia Dames, Daniel Berchtold, Katarzyna Winek, Luis Weitbrecht, Andreas Meisel and Christian Meisel
Vaccines 2020, 8(2), 253; https://doi.org/10.3390/vaccines8020253 - 28 May 2020
Cited by 4 | Viewed by 2973
Abstract
Pneumonia is the most frequent severe medical complication after stroke. An overactivation of the cholinergic signaling after stroke contributes to immunosuppression and the development of spontaneous pneumonia caused by Gram-negative pathogens. The α7 nicotinic acetylcholine receptor (α7nAChR) has already been identified as an [...] Read more.
Pneumonia is the most frequent severe medical complication after stroke. An overactivation of the cholinergic signaling after stroke contributes to immunosuppression and the development of spontaneous pneumonia caused by Gram-negative pathogens. The α7 nicotinic acetylcholine receptor (α7nAChR) has already been identified as an important mediator of the anti-inflammatory pathway after stroke. However, whether the α2, α5 and α9/10 nAChR expressed in the lung also play a role in suppression of pulmonary innate immunity after stroke is unknown. In the present study, we investigate the impact of various nAChRs on aspiration-induced pneumonia after stroke. Therefore, α2, α5, α7 and α9/10 nAChR knockout (KO) mice and wild type (WT) littermates were infected with Streptococcus pneumoniae (S. pneumoniae) three days after middle cerebral artery occlusion (MCAo). One day after infection pathogen clearance, cellularity in lung and spleen, cytokine secretion in bronchoalveolar lavage (BAL) and alveolar-capillary barrier were investigated. Here, we found that deficiency of various nAChRs does not contribute to an enhanced clearance of a Gram-positive pathogen causing post-stroke pneumonia in mice. In conclusion, these findings suggest that a single nAChR is not sufficient to mediate the impaired pulmonary defense against S. pneumoniae after experimental stroke. Full article
(This article belongs to the Special Issue Research on Innate Immunity and Inflammation)
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20 pages, 1976 KiB  
Article
HIV gp120 Induces the Release of Proinflammatory, Angiogenic, and Lymphangiogenic Factors from Human Lung Mast Cells
by Giancarlo Marone, Francesca Wanda Rossi, Antonio Pecoraro, Valentina Pucino, Gjada Criscuolo, Amato de Paulis, Giuseppe Spadaro, Gianni Marone and Gilda Varricchi
Vaccines 2020, 8(2), 208; https://doi.org/10.3390/vaccines8020208 - 3 May 2020
Cited by 23 | Viewed by 3082
Abstract
Human lung mast cells (HLMCs) express the high-affinity receptor FcεRI for IgE and are involved in chronic pulmonary diseases occurring at high frequency among HIV-infected individuals. Immunoglobulin superantigens bind to the variable regions of either the heavy or light chain of immunoglobulins (Igs). [...] Read more.
Human lung mast cells (HLMCs) express the high-affinity receptor FcεRI for IgE and are involved in chronic pulmonary diseases occurring at high frequency among HIV-infected individuals. Immunoglobulin superantigens bind to the variable regions of either the heavy or light chain of immunoglobulins (Igs). Glycoprotein 120 (gp120) of HIV-1 is a typical immunoglobulin superantigen interacting with the heavy chain, variable 3 (VH3) region of human Igs. The present study investigated whether immunoglobulin superantigen gp120 caused the release of different classes of proinflammatory and immunoregulatory mediators from HLMCs. The results show that gp120 from different clades induced the rapid (30 min) release of preformed mediators (histamine and tryptase) from HLMCs. gp120 also caused the de novo synthesis of cysteinyl leukotriene C4 (LTC4) and prostaglandin D2 (PGD2) from HLMCs. Incubation (6 h) of HLMC with gp120 induced the release of angiogenic (VEGF-A) and lymphangiogenic (VEGF-C) factors from HLMCs. The activating property of gp120 was mediated through the interaction with IgE VH3+ bound to FcεRI. Our data indicate that HIV gp120 is a viral superantigen, which induces the release of different proinflammatory, angiogenic, and lymphangiogenic factors from HLMCs. These observations could contribute to understanding, at least in part, the pathophysiology of chronic pulmonary diseases in HIV-infected individuals. Full article
(This article belongs to the Special Issue Research on Innate Immunity and Inflammation)
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16 pages, 2226 KiB  
Article
Sendai Virus, a Strong Inducer of Anti-Lentiviral State in Ovine Cells
by Lorena de Pablo-Maiso, Irache Echeverría, Sergio Rius-Rocabert, Lluís Luján, Dominique Garcin, Damián de Andrés, Estanislao Nistal-Villán and Ramsés Reina
Vaccines 2020, 8(2), 206; https://doi.org/10.3390/vaccines8020206 - 29 Apr 2020
Cited by 4 | Viewed by 4002
Abstract
Small ruminant lentiviruses (SRLVs) are widely spread in the ovine and caprine populations, causing an incurable disease affecting animal health and production. Vaccine development is hindered owing to the high genetic heterogeneity of lentiviruses and the selection of T-cell and antibody escape mutants, [...] Read more.
Small ruminant lentiviruses (SRLVs) are widely spread in the ovine and caprine populations, causing an incurable disease affecting animal health and production. Vaccine development is hindered owing to the high genetic heterogeneity of lentiviruses and the selection of T-cell and antibody escape mutants, requiring antigen delivery optimization. Sendai virus (SeV) is a respiratory paramyxovirus in mice that has been recognized as a potent inducer of innate immune responses in several species, including mouse and human. The aim of this study was to stimulate an innate antiviral response in ovine cells and evaluate the potential inhibitory effect upon small ruminant lentivirus (SRLV) infections. Ovine alveolar macrophages (AMs), blood-derived macrophages (BDMs), and skin fibroblasts (OSFs) were stimulated through infection with SeV encoding green fluorescent protein (GFP). SeV efficiently infected ovine cells, inducing an antiviral state in AM from SRLV naturally-infected animals, as well as in in vitro SRLV-infected BDM and OSF from non-infected animals. Supernatants from SeV-infected AM induced an antiviral state when transferred to fresh cells challenged with SRLV. Similar to SRLV, infectivity of an HIV-1-GFP lentiviral vector was also restricted in ovine cells infected with SeV. In myeloid cells, an M1-like proinflammatory polarization was observed together with an APOBEC3Z1 induction, among other lentiviral restriction factors. Our observations may boost new approximations in ameliorating the SRLV burden by stimulation of the innate immune response using SeV-based vaccine vectors. Full article
(This article belongs to the Special Issue Research on Innate Immunity and Inflammation)
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13 pages, 4349 KiB  
Article
In Ovo Delivered Toll-Like Receptor 7 Ligand, Resiquimod Enhances Host Responses against Infectious Bronchitis Corona Virus (IBV) Infection
by Upasama De Silva Senapathi, Mohamed Aboelkhair, Kekungu Puro, Mariam Ali, Aruna Amarasinghe, M. Sarjoon Abdul-Cader, Guido Van Marle, Markus Czub and Mohamed Faizal Abdul-Careem
Vaccines 2020, 8(2), 186; https://doi.org/10.3390/vaccines8020186 - 15 Apr 2020
Cited by 6 | Viewed by 3810
Abstract
Toll-like receptor (TLR) 7 ligand, resiquimod, has been studied as an adjuvant and antiviral agent against several pathogens in chicken. Yet, the effectiveness of resiquimod against infectious bronchitis virus (IBV) infection has not been evaluated. In this study, we investigated the effectiveness of [...] Read more.
Toll-like receptor (TLR) 7 ligand, resiquimod, has been studied as an adjuvant and antiviral agent against several pathogens in chicken. Yet, the effectiveness of resiquimod against infectious bronchitis virus (IBV) infection has not been evaluated. In this study, we investigated the effectiveness of resiquimod delivered pre-hatch (in ovo) against IBV infection post-hatch identifying key mechanisms involved in resiquimod driven immune activation. First, we found an upregulation of interleukin (IL)-1β and interferon (IFN)-γ mRNA levels and considerable expansions of macrophage and cluster of differentiation (CD) 8α+ T cell populations in lungs of chicken as early as day one post-hatch, following pre-hatch delivery of resiquimod. Second, we observed that resiquimod was able to act as an adjuvant when resiquimod was delivered pre-hatch along with an inactivated IBV vaccine. Finally, when the resiquimod pretreated one-day-old chickens were infected with IBV, reduction in viral shedding via oral and fecal routes was observed at 3 days post- infection. Overall, this study shows that the pre-hatch delivered resiquimod increases cell-mediated immune responses in lungs with an advantage of reduction in IBV shedding. Full article
(This article belongs to the Special Issue Research on Innate Immunity and Inflammation)
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17 pages, 1855 KiB  
Article
Downregulation of A20 Expression Increases the Immune Response and Apoptosis and Reduces Virus Production in Cells Infected by the Human Respiratory Syncytial Virus
by María Martín-Vicente, Rubén González-Sanz, Isabel Cuesta, Sara Monzón, Salvador Resino and Isidoro Martínez
Vaccines 2020, 8(1), 100; https://doi.org/10.3390/vaccines8010100 - 24 Feb 2020
Cited by 11 | Viewed by 4098
Abstract
Human respiratory syncytial virus (HRSV) causes severe lower respiratory tract infections in infants, the elderly, and immunocompromised adults. Regulation of the immune response against HRSV is crucial to limiting virus replication and immunopathology. The A20/TNFAIP3 protein is a negative regulator of nuclear factor [...] Read more.
Human respiratory syncytial virus (HRSV) causes severe lower respiratory tract infections in infants, the elderly, and immunocompromised adults. Regulation of the immune response against HRSV is crucial to limiting virus replication and immunopathology. The A20/TNFAIP3 protein is a negative regulator of nuclear factor kappa B (NF-κB) and interferon regulatory factors 3/7 (IRF3/7), which are key transcription factors involved in the inflammatory/antiviral response of epithelial cells to virus infection. Here, we investigated the impact of A20 downregulation or knockout on HRSV growth and the induction of the immune response in those cells. Cellular infections in which the expression of A20 was silenced by siRNAs or eliminated by gene knockout showed increased inflammatory/antiviral response and reduced virus production. Similar results were obtained when the expression of A20-interacting proteins, such as TAX1BP1 and ABIN1, was silenced. Additionally, downregulation of A20, TAX1BP1, and ABIN1 increased cell apoptosis in HRSV-infected cells. These results show that the downregulation of A20 expression might contribute in the control of HRSV infections by potentiating the early innate immune response and increasing apoptosis in infected cells. Full article
(This article belongs to the Special Issue Research on Innate Immunity and Inflammation)
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13 pages, 1358 KiB  
Article
Surface Immunogenic Protein of Streptococcus Group B is an Agonist of Toll-Like Receptors 2 and 4 and a Potential Immune Adjuvant
by Diego A. Diaz-Dinamarca, Ricardo A. Manzo, Daniel A. Soto, María José Avendaño-Valenzuela, Diego N. Bastias, Paulina I. Soto, Daniel F. Escobar, Valeria Vasquez-Saez, Flavio Carrión, Magdalena S. Pizarro-Ortega, Christian A. M. Wilson, Julio Berrios, Alexis M. Kalergis and Abel E. Vasquez
Vaccines 2020, 8(1), 29; https://doi.org/10.3390/vaccines8010029 - 16 Jan 2020
Cited by 7 | Viewed by 3476
Abstract
Vaccine-induced protection against pathogens, especially subunit-based vaccines, are related to antigen properties but mainly in their ability to stimulate the immune system by the use of an adjuvant. Modern vaccines are formulated with a high level of antigen purity, where an efficient adjuvant [...] Read more.
Vaccine-induced protection against pathogens, especially subunit-based vaccines, are related to antigen properties but mainly in their ability to stimulate the immune system by the use of an adjuvant. Modern vaccines are formulated with a high level of antigen purity, where an efficient adjuvant is necessary. In this context, the use of protein Toll-Like Receptor (TLR) agonists as vaccine adjuvants has been highlighted because of their optimal immunogenicity and minimal toxicity. The Surface Immunogenic Protein (SIP) from Group B Streptococcus (GBS) has gained importance as a new potential protein-based vaccine. Recently, we reported that recombinant SIP (rSIP) expressed by E. coli and purified by High Performance Liquid Chromatography (HPLC) alone induces a protective humoral immune response. In this study, we present the immunomodulatory properties of rSIP as a protein-based adjuvant, as an agonist of TLR. To this end, we showed that C57BL/6 bone marrow-derived dendritic cells pulsed by rSIP resulted in enhanced CD40, CD80, CD86, and Major Histocompatibility Complex (MHC) class II as well as increased secretion proinflammatory cytokines Interleukin (IL)-6, Interferon (IFN)-γ, Tumor Necrosis Factor (TNF)-α, and IL-10. Next, we investigated the in vivo effect of rSIP in the absence or presence of ovalbumin (OVA) on antigen-specific antibody secretion in C57BL/6 mice. Immunization with rSIP plus OVA showed that anti-OVA IgG2a and IgG1a increased significantly compared with OVA alone in C57BL/6 mice. Also, the immunization of rSIP plus OVA generates increased serum cytokines levels characterized by IL-12p70, IL-10, IL-4, and IFN-γ. Interestingly, we observed that rSIP stimulate Toll Like Receptor (TLR)2 and TLR4, individually expressed by Human embryonic kidney (HEK) 293-derived TLR reporter cells. These findings suggest that rSIP is a new potential protein TLR agonist adjuvant and may be employed in the development of new vaccines. Full article
(This article belongs to the Special Issue Research on Innate Immunity and Inflammation)
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28 pages, 9552 KiB  
Article
Polyamine Transport Protein PotD Protects Mice against Haemophilus parasuis and Elevates the Secretion of Pro-Inflammatory Cytokines of Macrophage via JNK–MAPK and NF–κB Signal Pathways through TLR4
by Ke Dai, Xiaoyu Ma, Zhen Yang, Yung-Fu Chang, Sanjie Cao, Qin Zhao, Xiaobo Huang, Rui Wu, Yong Huang, Qigui Yan, Xinfeng Han, Xiaoping Ma, Xintian Wen and Yiping Wen
Vaccines 2019, 7(4), 216; https://doi.org/10.3390/vaccines7040216 - 14 Dec 2019
Cited by 11 | Viewed by 3681
Abstract
The potD gene, belonging to the well-conserved ABC (ATP-binding cassette) transport system potABCD, encodes the bacterial substrate-binding subunit of the polyamine transport system. In this study, we found PotD in Haemophilus (Glaesserella) parasuis could actively stimulate both humoral immune and [...] Read more.
The potD gene, belonging to the well-conserved ABC (ATP-binding cassette) transport system potABCD, encodes the bacterial substrate-binding subunit of the polyamine transport system. In this study, we found PotD in Haemophilus (Glaesserella) parasuis could actively stimulate both humoral immune and cellular immune responses and elevate lymphocyte proliferation, thus eliciting a Th1-type immune response in a murine immunity and infection model. Stimulation of Raw 264.7 macrophages with PotD validated that Toll-like receptor 4, rather than 2, participated in the positive transcription and expression of pro-inflammatory cytokines IL–1β, IL–6, and TNF–α using qPCR and ELISA. Blocking signal-regulated JNK–MAPK and RelA(p65) pathways significantly decreased PotD-induced pro-inflammatory cytokine production. Overall, we conclude that vaccination of PotD could induce both humoral and cellular immune responses and provide immunoprotection against H. parasuis challenge. The data also suggest that Glaesserella PotD is a novel pro-inflammatory mediator and induces TLR4-dependent pro-inflammatory activity in Raw 264.7 macrophages through JNK–MAPK and RelA(p65) pathways. Full article
(This article belongs to the Special Issue Research on Innate Immunity and Inflammation)
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13 pages, 1762 KiB  
Article
Anti-Idiotype Vaccine Provides Protective Immunity Against Vibrio Harveyi in Grouper (Epinephelus Coioides)
by Wan-Ling Huang, Shu-Chun Chuang and Chung-Da Yang
Vaccines 2019, 7(4), 210; https://doi.org/10.3390/vaccines7040210 - 9 Dec 2019
Cited by 6 | Viewed by 3563
Abstract
Since anti-idiotype antibodies (anti-Id Abs) can display internal images similar to the epitopes of the original antigens, we aimed to produce an effective vaccine based on anti-Id Abs to protect grouper from Vibrio harveyi. Anti-Id IgG showing V. harveyi-like internal images [...] Read more.
Since anti-idiotype antibodies (anti-Id Abs) can display internal images similar to the epitopes of the original antigens, we aimed to produce an effective vaccine based on anti-Id Abs to protect grouper from Vibrio harveyi. Anti-Id IgG showing V. harveyi-like internal images was produced from rabbits immunized with the Id portion of grouper anti-V. harveyi antibodies and its Fab portion, anti-Id IgG (Fab), was then prepared to use as the anti-Id vaccine. The resulting anti-Id IgG (Fab) was intraperitoneally injected twice at a 21-day interval into grouper to evaluate its ability to induce effective anti-V. harveyi immunity and protection, in comparison with inactivated V. harveyi bacteria. We found that administration of grouper with anti-Id IgG (Fab) resulted in enhanced V. harveyi-specific serum titers, as well as lymphocyte proliferation. In addition, three weeks after boosting, 90% (18/20) of fish immunized with anti-Id IgG (Fab) survived at least 28 days after a lethal challenge of the heterologous, virulent strain of V. harveyi. The capability of this anti-Id IgG (Fab) to imitate the epitopes of V. harveyi antigens and effectively induce protective immunity would be advantageous for its application in developing an efficacious vaccine against V. harveyi for future farm use in fish. Full article
(This article belongs to the Special Issue Research on Innate Immunity and Inflammation)
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Review

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24 pages, 696 KiB  
Review
Innate Immune Response against Hepatitis C Virus: Targets for Vaccine Adjuvants
by Daniel Sepulveda-Crespo, Salvador Resino and Isidoro Martinez
Vaccines 2020, 8(2), 313; https://doi.org/10.3390/vaccines8020313 - 17 Jun 2020
Cited by 15 | Viewed by 4106
Abstract
Despite successful treatments, hepatitis C virus (HCV) infections continue to be a significant world health problem. High treatment costs, the high number of undiagnosed individuals, and the difficulty to access to treatment, particularly in marginalized susceptible populations, make it improbable to achieve the [...] Read more.
Despite successful treatments, hepatitis C virus (HCV) infections continue to be a significant world health problem. High treatment costs, the high number of undiagnosed individuals, and the difficulty to access to treatment, particularly in marginalized susceptible populations, make it improbable to achieve the global control of the virus in the absence of an effective preventive vaccine. Current vaccine development is mostly focused on weakly immunogenic subunits, such as surface glycoproteins or non-structural proteins, in the case of HCV. Adjuvants are critical components of vaccine formulations that increase immunogenic performance. As we learn more information about how adjuvants work, it is becoming clear that proper stimulation of innate immunity is crucial to achieving a successful immunization. Several hepatic cell types participate in the early innate immune response and the subsequent inflammation and activation of the adaptive response, principally hepatocytes, and antigen-presenting cells (Kupffer cells, and dendritic cells). Innate pattern recognition receptors on these cells, mainly toll-like receptors, are targets for new promising adjuvants. Moreover, complex adjuvants that stimulate different components of the innate immunity are showing encouraging results and are being incorporated in current vaccines. Recent studies on HCV-vaccine adjuvants have shown that the induction of a strong T- and B-cell immune response might be enhanced by choosing the right adjuvant. Full article
(This article belongs to the Special Issue Research on Innate Immunity and Inflammation)
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23 pages, 654 KiB  
Review
Primary Sjogren Syndrome: Focus on Innate Immune Cells and Inflammation
by Chiara Rizzo, Giulia Grasso, Giulia Maria Destro Castaniti, Francesco Ciccia and Giuliana Guggino
Vaccines 2020, 8(2), 272; https://doi.org/10.3390/vaccines8020272 - 3 Jun 2020
Cited by 20 | Viewed by 5620
Abstract
Primary Sjogren Syndrome (pSS) is a complex, multifactorial rheumatic disease that mainly targets salivary and lacrimal glands, inducing epithelitis. The cause behind the autoimmunity outbreak in pSS is still elusive; however, it seems related to an aberrant reaction to exogenous triggers such as [...] Read more.
Primary Sjogren Syndrome (pSS) is a complex, multifactorial rheumatic disease that mainly targets salivary and lacrimal glands, inducing epithelitis. The cause behind the autoimmunity outbreak in pSS is still elusive; however, it seems related to an aberrant reaction to exogenous triggers such as viruses, combined with individual genetic pre-disposition. For a long time, autoantibodies were considered as the hallmarks of this disease; however, more recently the complex interplay between innate and adaptive immunity as well as the consequent inflammatory process have emerged as the main mechanisms of pSS pathogenesis. The present review will focus on innate cells and on the principal mechanisms of inflammation connected. In the first part, an overview of innate cells involved in pSS pathogenesis is provided, stressing in particular the role of Innate Lymphoid Cells (ILCs). Subsequently we have highlighted the main inflammatory pathways, including intra- and extra-cellular players. A better knowledge of such processes could determine the detection of new therapeutic targets that are a major need for pSS. Full article
(This article belongs to the Special Issue Research on Innate Immunity and Inflammation)
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