Topic Editors

Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Shenzhen, China
Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO, USA

The Role of Innate Lymphocytes in Infection and Host Immunity

Abstract submission deadline
closed (30 June 2022)
Manuscript submission deadline
closed (31 August 2022)
Viewed by
36989

Topic Information

Dear Colleagues,

The innate and adaptive immune systems have evolved to sense infections and limit disease severity. Bridging these two systems, innate lymphocytes circulating in the periphery or residing in tissues and mucosal barriers are poised to mount rapid immune responses. The class of innate lymphocytes is broad, including those that express germline-encoded antigen receptors, e.g., innate lymphoid cells (ILCs) and natural killer (NK) cells, and those that express antigen receptors that undergo somatic recombination, e.g., mucosal-associated invariant T (MAIT) cells, natural killer T (NKT) cells, γδ T cells, and innate B cells.

The receptors of innate lymphocytes can recognise a variety of antigenic structures; some subsets can engage with peptide-bound classical major histocompatibility complexes (MHC) or nonpeptide antigens that are presented by nonclassical MHC proteins or are indirectly activated through the actions of cytokines. Their abundant numbers at mucosal surfaces and their rapid effector function renders these specialised immune cells as an ideal first-line defence against invading pathogens. Although they may provide critical effector roles during infections, their rapid responses can also contribute to disease pathogenesis.

The aim of this Topic is to explore the contributions of innate lymphocytes in bacterial, fungal, and viral infections and host immunity. We encourage the submission of all types of manuscripts (e.g., reviews, research articles, and short communications) pertaining to pathogen interactions with innate lymphocyte populations and the ensuing host immunity, including but not limited to the following topics:

  • Antimicrobial mechanisms of innate lymphocytes;
  • Mechanisms of surveillance against bacterial, fungal, and viral infections;
  • Microbial mechanisms of immune evasion;
  • Microbial immunopathogenesis and immunopathology;
  • Pathogen–host interactions, including co-evolution of pathogens and host defence factors, immune exhaustion, and microbial latency;
  • Innate lymphocyte-based vaccination strategies and antimicrobial immunotherapies;
  • Emerging and zoonotic infectious diseases and innate lymphocyte interactions;
  • Resolution of microbial infections.

Dr. Edwin Leeansyah
Dr. Liyen Loh
Topic Editors

Keywords

  • mucosal immunity
  • innate lymphoid cells (ILCs)
  • mucosal-associated invariant T (MAIT)
  • antiviral response
  • natural killer cells (NKT)
  • innate lymphoid cells
  • major histocompatibility complexes (MHC)
  • γδ T cells
  • cytokines
  • emerging and zoonotic
  • immune evasion
  • antimicrobial mechanisms
  • microbial immunopathogenesis
  • microbial immunopathology
  • pathogen–host interactions
  • immune exhaustion
  • microbial latency
  • vaccination strategies
  • SARS-CoV-2

Participating Journals

Journal Name Impact Factor CiteScore Launched Year First Decision (median) APC
Viruses
viruses
3.8 7.3 2009 16.1 Days CHF 2600
International Journal of Molecular Sciences
ijms
4.9 8.1 2000 18.1 Days CHF 2900
Journal of Fungi
jof
4.2 6.7 2015 17.1 Days CHF 2600
Microorganisms
microorganisms
4.1 7.4 2013 13.4 Days CHF 2700
Microbiology Research
microbiolres
2.1 1.9 2010 16.7 Days CHF 1600

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Published Papers (8 papers)

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15 pages, 2555 KiB  
Article
Selective Expansion of NKG2C+ Adaptive NK Cells Using K562 Cells Expressing HLA-E
by Minh-Trang Thi Phan, Jinho Kim, Seung Kwon Koh, Yuree Lim, Hongbi Yu, Mijeong Lee, Jong-Min Lee, Eun-Suk Kang, Hyun-Young Kim, Sang-Ki Kim, Ilwoong Hwang and Duck Cho
Int. J. Mol. Sci. 2022, 23(16), 9426; https://doi.org/10.3390/ijms23169426 - 20 Aug 2022
Cited by 3 | Viewed by 3488
Abstract
Adaptive natural killer (NK) cells expressing self-specific inhibitory killer-cell immunoglobulin-like receptors (KIRs) can be expanded in vivo in response to human cytomegalovirus (HCMV) infection. Developing a method to preferentially expand this subset is essential for effective targeting of allogeneic cancer cells. A previous [...] Read more.
Adaptive natural killer (NK) cells expressing self-specific inhibitory killer-cell immunoglobulin-like receptors (KIRs) can be expanded in vivo in response to human cytomegalovirus (HCMV) infection. Developing a method to preferentially expand this subset is essential for effective targeting of allogeneic cancer cells. A previous study developed an in vitro method to generate single KIR+ NK cells for enhanced targeting of the primary acute lymphoblastic leukemia cells; however, the expansion rate was quite low. Here, we present an effective expansion method using genetically modified K562-HLA-E feeder cells for long-term proliferation of adaptive NK cells displaying highly differentiated phenotype and comparable cytotoxicity, CD107a, and interferon-γ (IFN-γ) production. More importantly, our expansion method achieved more than a 10,000-fold expansion of adaptive NK cells after 6 weeks of culture, providing a high yield of alloreactive NK cells for cell therapy against cancer. Full article
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20 pages, 3565 KiB  
Article
Revealing the Immune Heterogeneity between Systemic Lupus Erythematosus and Rheumatoid Arthritis Based on Multi-Omics Data Analysis
by Yuntian Zhang and Tzong-Yi Lee
Int. J. Mol. Sci. 2022, 23(9), 5166; https://doi.org/10.3390/ijms23095166 - 5 May 2022
Cited by 22 | Viewed by 6355
Abstract
The pathogenesis of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are greatly influenced by different immune cells. Nowadays both T-cell receptor (TCR) and B-cell receptor (BCR) sequencing technology have emerged with the maturity of NGS technology. However, both SLE and RA peripheral [...] Read more.
The pathogenesis of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are greatly influenced by different immune cells. Nowadays both T-cell receptor (TCR) and B-cell receptor (BCR) sequencing technology have emerged with the maturity of NGS technology. However, both SLE and RA peripheral blood TCR or BCR repertoire sequencing remains lacking because repertoire sequencing is an expensive assay and consumes valuable tissue samples. This study used computational methods TRUST4 to construct TCR repertoire and BCR repertoire from bulk RNA-seq data of both SLE and RA patients’ peripheral blood and analyzed the clonality and diversity of the immune repertoire between the two diseases. Although the functions of immune cells have been studied, the mechanism is still complicated. Differentially expressed genes in each immune cell type and cell–cell interactions between immune cell clusters have not been covered. In this work, we clustered eight immune cell subsets from original scRNA-seq data and disentangled the characteristic alterations of cell subset proportion under both SLE and RA conditions. The cell–cell communication analysis tool CellChat was also utilized to analyze the influence of MIF family and GALECTIN family cytokines, which were reported to regulate SLE and RA, respectively. Our findings correspond to previous findings that MIF increases in the serum of SLE patients. This work proved that the presence of LGALS9, PTPRC and CD44 in platelets could serve as a clinical indicator of rheumatoid arthritis. Our findings comprehensively illustrate dynamic alterations in immune cells during pathogenesis of SLE and RA. This work identified specific V genes and J genes in TCR and BCR that could be used to expand our understanding of SLE and RA. These findings provide a new insight inti the diagnosis and treatment of the two autoimmune diseases. Full article
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19 pages, 1446 KiB  
Review
Innate Lymphoid Cells: Emerging Players in Pancreatic Disease
by Saimeng Shi, Longyun Ye, Kaizhou Jin, Zhiwen Xiao, Xianjun Yu and Weiding Wu
Int. J. Mol. Sci. 2022, 23(7), 3748; https://doi.org/10.3390/ijms23073748 - 29 Mar 2022
Cited by 5 | Viewed by 4857
Abstract
Common pancreatic diseases have caused significant economic and social burdens worldwide. The interstitial microenvironment is involved in and plays a crucial part in the occurrence and progression of pancreatic diseases. Innate lymphoid cells (ILCs), an innate population of immune cells which have only [...] Read more.
Common pancreatic diseases have caused significant economic and social burdens worldwide. The interstitial microenvironment is involved in and plays a crucial part in the occurrence and progression of pancreatic diseases. Innate lymphoid cells (ILCs), an innate population of immune cells which have only gradually entered our visual field in the last 10 years, play an important role in maintaining tissue homeostasis, regulating metabolism, and participating in regeneration and repair. Recent evidence indicates that ILCs in the pancreas, as well as in other tissues, are also key players in pancreatic disease and health. Herein, we examined the possible functions of different ILC subsets in common pancreatic diseases, including diabetes mellitus, pancreatitis and pancreatic cancer, and discussed the potential practical implications of the relevant findings for future further treatment of these pancreatic diseases. Full article
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19 pages, 1321 KiB  
Review
Potential Utility of Natural Killer Cells for Eliminating Cells Harboring Reactivated Latent HIV-1 Following the Removal of CD8+ T Cell-Mediated Pro-Latency Effect(s)
by Georges Khoury, Deanna A. Kulpa and Matthew S. Parsons
Viruses 2021, 13(8), 1451; https://doi.org/10.3390/v13081451 - 26 Jul 2021
Viewed by 2493
Abstract
An impediment to curing HIV-1 infection is the persistence of latently infected cells in ART-treated people living with HIV (PLWH). A key strategy for curing HIV-1 infection is to activate transcription and translation of latent virus using latency reversing agents (LRAs) and eliminate [...] Read more.
An impediment to curing HIV-1 infection is the persistence of latently infected cells in ART-treated people living with HIV (PLWH). A key strategy for curing HIV-1 infection is to activate transcription and translation of latent virus using latency reversing agents (LRAs) and eliminate cells harboring reactivated virus via viral cytopathic effect or immune clearance. In this review, we provide an overview of available LRAs and their use in clinical trials. Furthermore, we describe recent data suggesting that CD8+ T cells promote HIV-1 latency in the context of ART, even in the presence of LRAs, which might at least partially explain the clinical inefficiency of previous “shock and kill” trials. Here, we propose a novel cure strategy called “unlock, shock, disarm, and kill”. The general premise of this strategy is to shut down the pro-latency function(s) of CD8+ T cells, use LRAs to reverse HIV-1 latency, counteract anti-apoptotic molecules, and engage natural killer (NK) cells to mediate the killing of cells harboring reactivated latent HIV-1. Full article
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11 pages, 305 KiB  
Review
Monkeying around with MAIT Cells: Studying the Role of MAIT Cells in SIV and Mtb Co-Infection
by Ryan V. Moriarty, Amy L. Ellis and Shelby L. O’Connor
Viruses 2021, 13(5), 863; https://doi.org/10.3390/v13050863 - 8 May 2021
Cited by 2 | Viewed by 2955
Abstract
There were an estimated 10 million new cases of tuberculosis (TB) disease in 2019. While over 90% of individuals successfully control Mycobacterium tuberculosis (Mtb) infection, which causes TB disease, HIV co-infection often leads to active TB disease. Despite the co-endemic nature of HIV [...] Read more.
There were an estimated 10 million new cases of tuberculosis (TB) disease in 2019. While over 90% of individuals successfully control Mycobacterium tuberculosis (Mtb) infection, which causes TB disease, HIV co-infection often leads to active TB disease. Despite the co-endemic nature of HIV and TB, knowledge of the immune mechanisms contributing to the loss of control of Mtb replication during HIV infection is lacking. Mucosal-associated invariant T (MAIT) cells are innate-like T cells that target and destroy bacterially-infected cells and may contribute to the control of Mtb infection. Studies examining MAIT cells in human Mtb infection are commonly performed using peripheral blood samples. However, because Mtb infection occurs primarily in lung tissue and lung-associated lymph nodes, these studies may not be fully translatable to the tissues. Additionally, studies longitudinally examining MAIT cell dynamics during HIV/Mtb co-infection are rare, and lung and lymph node tissue samples from HIV+ patients are typically unavailable. Nonhuman primates (NHP) provide a model system to characterize MAIT cell activity during Mtb infection, both in Simian Immunodeficiency Virus (SIV)-infected and SIV-naïve animals. Using NHPs allows for a more comprehensive understanding of tissue-based MAIT cell dynamics during infection with both pathogens. NHP SIV and Mtb infection is similar to human HIV and Mtb infection, and MAIT cells are phenotypically similar in humans and NHPs. Here, we discuss current knowledge surrounding MAIT cells in SIV and Mtb infection, how SIV infection impairs MAIT cell function during Mtb co-infection, and knowledge gaps to address. Full article
22 pages, 1004 KiB  
Review
The Role of NK Cells in EBV Infection and EBV-Associated NPC
by Yi Tian Png, Audrey Zhi Yi Yang, Mei Ying Lee, Magdalene Jahn May Chua and Chwee Ming Lim
Viruses 2021, 13(2), 300; https://doi.org/10.3390/v13020300 - 15 Feb 2021
Cited by 21 | Viewed by 5032
Abstract
A vast majority of the population worldwide are asymptomatic carriers of Epstein-Barr Virus (EBV). However, some infected individuals eventually develop EBV-related cancers, including Nasopharyngeal Carcinoma (NPC). NPC is one of the most common EBV-associated epithelial cancers, and is highly prevalent in Southern China [...] Read more.
A vast majority of the population worldwide are asymptomatic carriers of Epstein-Barr Virus (EBV). However, some infected individuals eventually develop EBV-related cancers, including Nasopharyngeal Carcinoma (NPC). NPC is one of the most common EBV-associated epithelial cancers, and is highly prevalent in Southern China and Southeast Asia. While NPC is highly sensitive to radiotherapy and chemotherapy, there is a lack of effective and durable treatment among the 15%–30% of patients who subsequently develop recurrent disease. Natural Killer (NK) cells are natural immune lymphocytes that are innately primed against virus-infected cells and nascent aberrant transformed cells. As EBV is found in both virally infected and cancer cells, it is of interest to examine the NK cells’ role in both EBV infection and EBV-associated NPC. Herein, we review the current understanding of how EBV-infected cells are cleared by NK cells, and how EBV can evade NK cell-mediated elimination in the context of type II latency in NPC. Next, we summarize the current literature about NPC and NK cell biology. Finally, we discuss the translational potential of NK cells in NPC. This information will deepen our understanding of host immune interactions with EBV-associated NPC and facilitate development of more effective NK-mediated therapies for NPC treatment. Full article
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18 pages, 3791 KiB  
Article
Mucosal-Associated Invariant T (MAIT) Cells Are Highly Activated and Functionally Impaired in COVID-19 Patients
by Sebastian Deschler, Juliane Kager, Johanna Erber, Lisa Fricke, Plamena Koyumdzhieva, Alexandra Georgieva, Tobias Lahmer, Johannes R. Wiessner, Florian Voit, Jochen Schneider, Julia Horstmann, Roman Iakoubov, Matthias Treiber, Christof Winter, Jürgen Ruland, Dirk H. Busch, Percy A. Knolle, Ulrike Protzer, Christoph D. Spinner, Roland M. Schmid, Michael Quante and Katrin Böttcheradd Show full author list remove Hide full author list
Viruses 2021, 13(2), 241; https://doi.org/10.3390/v13020241 - 3 Feb 2021
Cited by 29 | Viewed by 4980
Abstract
Coronavirus disease 2019 (COVID-19), caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), comprises mild courses of disease as well as progression to severe disease, characterised by lung and other organ failure. The immune system is considered to play a crucial [...] Read more.
Coronavirus disease 2019 (COVID-19), caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), comprises mild courses of disease as well as progression to severe disease, characterised by lung and other organ failure. The immune system is considered to play a crucial role for the pathogenesis of COVID-19, although especially the contribution of innate-like T cells remains poorly understood. Here, we analysed the phenotype and function of mucosal-associated invariant T (MAIT) cells, innate-like T cells with potent antimicrobial effector function, in patients with mild and severe COVID-19 by multicolour flow cytometry. Our data indicate that MAIT cells are highly activated in patients with COVID-19, irrespective of the course of disease, and express high levels of proinflammatory cytokines such as IL-17A and TNFα ex vivo. Of note, expression of the activation marker HLA-DR positively correlated with SAPS II score, a measure of disease severity. Upon MAIT cell-specific in vitro stimulation, MAIT cells however failed to upregulate expression of the cytokines IL-17A and TNFα, as well as cytolytic proteins, that is, granzyme B and perforin. Thus, our data point towards an altered cytokine expression profile alongside an impaired antibacterial and antiviral function of MAIT cells in COVID-19 and thereby contribute to the understanding of COVID-19 immunopathogenesis. Full article
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18 pages, 8866 KiB  
Article
Longitudinal Analysis of Peripheral and Colonic CD161+ CD4+ T Cell Dysfunction in Acute HIV-1 Infection and Effects of Early Treatment Initiation
by Kerri G. Lal, Yuwadee Phuang-Ngern, Suchada Suhkumvittaya, Edwin Leeansyah, Aljawharah Alrubayyi, Joana Dias, Adam Waickman, Dohoon Kim, Eugène Kroon, Suteeraporn Pinyakorn, Leigh Anne Eller, Milton Maciel Jr., Rungsun Rerknimitr, Nitiya Chomchey, Nittaya Phanuphak, Mark S. de Souza, Sorachai Nitayaphan, Julie A. Ake, Sandhya Vasan, Merlin L. Robb, Jintanat Ananworanich, Johan K. Sandberg, Alexandra Schuetz, Michael A. Eller, Dominic Paquin-Proulx and on behalf of the RV217, RV254/SEARCH010, RV304/SEARCH Study Groupsadd Show full author list remove Hide full author list
Viruses 2020, 12(12), 1426; https://doi.org/10.3390/v12121426 - 11 Dec 2020
Cited by 3 | Viewed by 3019
Abstract
CD161 expression on CD4+ T cells is associated with a Th17 functional phenotype, as well as with an innate capacity to respond to interleukin (IL)-12 and IL-18 without T cell receptor (TCR) stimulation. Chronic HIV-1 infection is associated with loss of the [...] Read more.
CD161 expression on CD4+ T cells is associated with a Th17 functional phenotype, as well as with an innate capacity to respond to interleukin (IL)-12 and IL-18 without T cell receptor (TCR) stimulation. Chronic HIV-1 infection is associated with loss of the CD161+ CD4 T cell population, and non-human primate studies suggest that their depletion is associated with disease progression. However, the dynamics of the CD161+ CD4+ T cell population during acute HIV-1 infection remains unknown. In this study, we characterize peripheral blood CD161+ CD4+ T cells in detail, and examine how they are affected during the earliest stages of HIV-1 infection. Unbiased surface proteome screening and principal component analysis indicated that CD161+ CD4+ T cells are relatively phenotypically homogeneous between donors, and are intermediates between conventional CD4 T cells and innate-like T cells. In acute untreated HIV-1 infection, the circulating CD161+ CD4+ T cell population decreased in frequency, as did absolute cell counts starting from peak viral load, with elevated levels of activation and exhaustion markers expressed throughout acute HIV-1 infection. The capacity of these cells to respond to stimulation with IL-12 and IL-18 was also reduced. Early initiation of anti-retroviral treatment (ART) during acute HIV-1 infection restored the functionality of peripheral blood CD161+ CD4+ T cells, but not their frequency. In contrast, early ART initiation prevented the decline of colonic CD161+ CD4+ T cells that otherwise started during acute infection. Furthermore, loss of peripheral and colonic CD161+ CD4+ T cells in untreated infection was associated with levels of viral load. These results suggest that acute HIV-1 infection has profound effects on the CD161+ CD4+ T cell population that could not be completely prevented by the initiation of ART. Full article
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