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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Microbiology".

Deadline for manuscript submissions: closed (20 April 2025) | Viewed by 11246

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Special Issue Editor

Prof. Dr. Piotr Bąska

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Guest Editor

Division of Pharmacology and Toxicology, Department of Preclinical Sciences, Institute of Veterinary Medicine, Warsaw University of Life Sciences, 02-786 Warsaw, Poland
Interests: immunology; microbiology; veterinary; biochemistry
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Parasites are a divergent group of organisms that attack various hosts, leading to serious problems for both human and veterinary medicine. They lead to significant morbidity and losses in animal production. Clinical manifestations can range from severe and fatal to long-lasting infections that have a beneficial impact on the host, alleviating symptoms of allergies and autoimmune diseases. Substantial focus has been placed on investigating both the positive and negative aspects of these infections. Scientists have been trying for years to develop effective vaccines against parasites as well as to utilize them in the treatment of autoimmune diseases and allergies. However, in order to achieve these goals, deciphering the molecular-level crosstalk between invading parasites and the host is necessary. Parasites can interfere with the immune system, interact with the nervous system, and impact the composition of the host's microbiota.

The purpose of this issue is to explore the knowledge regarding both the positive and negative aspects of parasitic infections. It welcomes, but is not limited to, manuscripts related to vaccine development and the understanding of interactions with the immune system. Studies investigating the interplay between parasites and the nervous or hormonal systems, as well as other components of the host response, are also of special interest.

Dr. Piotr Bąska
Guest Editor

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Keywords

parasites
immune response
immunomodulation
vaccines
helminths
nervous system and parasitic infection

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Published Papers (6 papers)

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Research

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18 pages, 1733 KiB

Open AccessArticle

The Trivalent Recombinant Chimeric Proteins Containing Immunodominant Fragments of Toxoplasma gondii SAG1 and SAG2 Antigens in Their Core—A Good Diagnostic Tool for Detecting IgG Antibodies in Human Serum Samples

by Bartłomiej Tomasz Ferra, Maciej Chyb, Marta Skwarecka and Justyna Gatkowska

Int. J. Mol. Sci. 2025, 26(12), 5621; https://doi.org/10.3390/ijms26125621 - 12 Jun 2025

Viewed by 340

Abstract

Toxoplasmosis is one of the most common and neglected parasitic diseases caused by the intracellular parasite Toxoplasma gondii. The parasitic invasion in humans is associated with certain problems, such as the lack of effective immunoprophylaxis or a complex diagnostic algorithm, which require continuous improvement. Both problems can be overcome by the recent development of T. gondii proteomics, which has allowed the design of different recombinant antigens. In this study we evaluated the potential usefulness of nineteen recombinant chimeric T. gondii proteins for serodiagnosis. A chimeric antigen composed of the surface antigens SAG1-SAG2 was developed and used as the basis for the generation of 18 subsequent trivalent chimeric antigens containing different immunodominant fragments of the parasite proteins. The recombinant antigens were used in an indirect enzyme-linked immunosorbent assay (ELISA) test to evaluate their ability to detect specific IgG antibodies in human sera. A total of 338 human sera were analyzed to assess the sensitivity and specificity of the tests. Sixteen of the antigens tested demonstrated 100% sensitivity and specificity in the ELISA for the detection of specific IgG antibodies. These results provide an optimistic outlook for the potential replacement of the currently used native antigen mix with recombinant antigens in human T. gondii serodiagnostics. Full article

(This article belongs to the Special Issue Molecular Research on Host-Parasite Interactions)

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19 pages, 7640 KiB

Open AccessArticle

Leveraging the Polymorphism of the Merozoite Surface Protein 2 (MSP2) to Engineer Molecular Tools for Predicting Malaria Episodes in a Community

by Edgar Mutebwa Kalimba, Sandra Fankem Noukimi, Jean-Bosco Mbonimpa, Cabirou Mounchili Shintouo, Radouane Ouali, Mariama Telly Diallo, Antoine Vicario, Samuel Vandecasteele, Abenwie Suh Nchang, Lahngong Methodius Shinyuy, Mary Teke Efeti, Aimee Nadine Nsengiyumva Ishimwe, Aloysie Basoma Biryuwenze, Arsene Musana Habimana, Louis de Mont Fort Ntwali Mugisha, Sara Ayadi, Robert Adamu Shey, Rose Njemini, Stephen Mbigha Ghogomu and Jacob Souopgui

Int. J. Mol. Sci. 2025, 26(11), 5277; https://doi.org/10.3390/ijms26115277 - 30 May 2025

Viewed by 540

Abstract

Malaria remains a significant public health challenge, particularly in endemic regions. The extensive genetic diversity of Plasmodium falciparum (Pf) complicates outbreak prediction and transmission control. One of its most polymorphic markers, merozoite surface protein 2 (MSP2), presents a potential target for molecular surveillance. This cross-sectional study, conducted at King Faisal Hospital Rwanda (KFHR) from October 2021 to June 2023, assessed MSP2’s utility in malaria prediction. PfMSP2 was sequenced, and selected amplicons were cloned, expressed in bacteria, and purified. These antigens were tested against sera from malaria patients and geographically diverse healthy individuals, with complementary surveys contextualizing serological findings. Of the 75 processed monoallelic clinical isolates, 3D7 strains predominated over FC27. Three MSP2-derived biomarkers were produced, eliciting significantly low IgG responses in malaria patients and Belgian controls, but a complex pattern emerged in healthy individuals, with significant differences between Rwandan and Cameroonian samples. IgG3 was the predominant subclass in individuals with high IgG responses. Notably, Rwandan individuals with weak humoral responses to the tested antigens but also other with high responses experienced malaria episodes in the subsequent year. These findings highlight MSP2 polymorphism as a valuable tool for malaria surveillance and outbreak prediction. Integrating genotyping and serology could enable precise, community-specific malaria risk assessments, strengthening control strategies. Full article

(This article belongs to the Special Issue Molecular Research on Host-Parasite Interactions)

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19 pages, 2850 KiB

Open AccessArticle

The Impact of Cell-Intrinsic STAT6 Protein on Donor T Cell-Mediated Graft-Versus-Tumor Effect

by Xiaoqun Guan, Hope Fury, Priya D. Issuree, Tyler Atagozli, Emory E. McManimon, Peng Shao, Yue Li, Michael Chimenti, Noah S. Butler, Mark H. Kaplan, David E. Elliott, Bruce R. Blazar and M. Nedim Ince

Int. J. Mol. Sci. 2025, 26(1), 280; https://doi.org/10.3390/ijms26010280 - 31 Dec 2024

Viewed by 1387

Abstract

Bone marrow transplantation (BMT) is mainly performed to restore an anti-tumor immune response, called the graft-versus-tumor (GVT) effect, against leukemia, myeloma and lymphoma. This GVT reactivity is driven by donor T cells, and it can also cause lethal graft-versus-host disease (GVHD). We previously demonstrated that the colonization of mice with helminths preserves the GVT response while suppressing GVHD. As the T helper-2 (Th2) pathway is critical to helminthic immune regulation, we asked whether the genetic induction of Th2 signaling in donor T cells can restore helminthic immune regulation after BMT. Our studies utilized transgenic donor T lymphocytes that overexpress a constitutively active form of the Th2-associated transcription factor STAT6. Constitutively active STAT6 sustained the GVT response without causing severe acute GVHD, where transgenic T cells generated robust quantities of cytotoxic proteins important in GVT response, such as granzymes A and B, interferon-γ and Fas ligand, in addition to generating high quantities of Th2/regulatory cytokines. Bioinformatic analysis based on chromosome immune precipitation experiments indicated that STAT6 stimulates the expression of granzymes directly. Thus, in preserving the GVT response without causing GVHD mortality, our results indicate the therapeutic potential of restoring helminthic immune modulation by targeting STAT6 and STAT6-dependent T cell maturation. Full article

(This article belongs to the Special Issue Molecular Research on Host-Parasite Interactions)

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14 pages, 3970 KiB

Open AccessArticle

Functional Characterization of Six Eukaryotic Translation Initiation Factors of Toxoplasma gondii Using the CRISPR-Cas9 System

by Yong-Jie Kou, Jin Gao, Rui Li, Zhi-Ya Ma, Hany M. Elsheikha, Xiao-Jing Wu, Xiao-Nan Zheng, Meng Wang and Xing-Quan Zhu

Int. J. Mol. Sci. 2024, 25(14), 7834; https://doi.org/10.3390/ijms25147834 - 17 Jul 2024

Viewed by 1435

Abstract

Eukaryotic translation initiation factors (eIFs) are crucial for initiating protein translation and ensuring the correct assembly of mRNA-ribosomal subunit complexes. In this study, we investigated the effects of deleting six eIFs in the apicomplexan parasite Toxoplasma gondii using the CRISPR-Cas9 system. We determined the subcellular localization of these eIFs using C-terminal endogenous tagging and immunofluorescence analysis. Four eIFs (RH::315150-6HA, RH::286090-6HA, RH::249370-6HA, and RH::211410-6HA) were localized in the cytoplasm, while RH::224235-6HA was localized in the apicoplast. Additionally, RH::272640-6HA was found in both the basal complex and the cytoplasm of T. gondii. Functional characterization of the six RHΔeIFs strains was conducted using plaque assay, cell invasion assay, intracellular growth assay and egress assay in vitro, and virulence assay in mice. Disruption of five eIF genes (RHΔ315150, RHΔ272640, RHΔ249370, RHΔ211410, and RHΔ224235) did not affect the ability of the T. gondii RH strain to invade, replicate, form plaques and egress in vitro, or virulence in Kunming mice (p > 0.05). However, the RHΔ286090 strain showed slightly reduced invasion efficiency and virulence (p < 0.01) compared to the other five RHΔeIFs strains and the wild-type strain. The disruption of the TGGT1_286090 gene significantly impaired the ability of tachyzoites to differentiate into bradyzoites in both type I RH and type II Pru strains. These findings reveal that the eukaryotic translation initiation factor TGGT1_286090 is crucial for T. gondii bradyzoite differentiation and may serve as a potential target for drug development and an attenuated vaccine against T. gondii. Full article

(This article belongs to the Special Issue Molecular Research on Host-Parasite Interactions)

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14 pages, 2504 KiB

Open AccessArticle

Assessment of the Immunoprotective Efficacy of Recombinant 14-3-3 Protein and Dense Granule Protein 10 (GRA10) as Candidate Antigens for Rabbit Vaccines against Eimeria intestinalis

by Changming Xiong, Wei He, Jie Xiao, Ge Hao, Jiayan Pu, Hao Chen, Liwen Xu, Yuhua Zhu and Guangyou Yang

Int. J. Mol. Sci. 2023, 24(19), 14418; https://doi.org/10.3390/ijms241914418 - 22 Sep 2023

Cited by 5 | Viewed by 2073

Abstract

Eimeria intestinalis infects rabbits, causing severe intestinal coccidiosis. Prolonged anticoccidial drug use might lead to coccidia resistance and drug residues in food. Thus, vaccines are required to control rabbit coccidiosis. In this study, recombinant E. intestinalis 14-3-3 and GRA10 proteins (rEi-14-3-3 and rEi-GRA10) were obtained via prokaryotic expression and used as recombinant subunit vaccines. Fifty 30-day-old rabbits were randomly grouped as follows: PBS-uninfected group, PBS-infected group, Trx-His-S control group, and rEi-14-3-3 and rEi-GRA10 immunized groups. The rabbits were subcutaneously immunized twice at 2-week intervals, challenged with 7 × 10⁴ sporulated oocysts, and sacrificed 14 days later. The protective effects were assessed via clinical signs, relative weight gain, oocyst reduction, mean intestinal lesion score, ACI (anticoccidial index), cytokine, and specific antibody levels in sera. The rEi-14-3-3 and rEi-GRA10 groups had higher relative weight gain rates of 81.94% and 73.61% (p < 0.05), and higher oocyst reduction rates of 86.13% and 84.87% (p < 0.05), respectively. The two immunized groups had fewer intestinal lesions (p < 0.05) and higher IgG levels (p < 0.05). Higher levels of IL-2, IL-4, and IFN-γ cytokines in the rEi-14-3-3 group (p < 0.05) and a higher level of IFN-γ in the rEi-GRA10 group (p < 0.05) were observed. The ACI values of the rEi-14-3-3 and rEi-GRA10 groups were 168.24 and 159.91, with good and moderate protective effects, respectively. Both rEi-14-3-3 and rEi-GRA10 induced humoral immunity in the rabbits. In addition, rEi-14-3-3 induced Th1- and Th2-type immune responses. Both recombinant proteins were protective against E. intestinalis infection in rabbits, with rEi-14-3-3 showing a better protective effect. Full article

(This article belongs to the Special Issue Molecular Research on Host-Parasite Interactions)

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Review

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22 pages, 1675 KiB

Open AccessReview

The Roles of Various Immune Cell Populations in Immune Response against Helminths

by Janina Lekki-Jóźwiak and Piotr Bąska

Int. J. Mol. Sci. 2024, 25(1), 420; https://doi.org/10.3390/ijms25010420 - 28 Dec 2023

Cited by 5 | Viewed by 4233

Abstract

Helminths are multicellular parasites that are a substantial problem for both human and veterinary medicine. According to estimates, 1.5 billion people suffer from their infection, resulting in decreased life quality and burdens for healthcare systems. On the other hand, these infections may alleviate autoimmune diseases and allergy symptoms. The immune system is programmed to combat infections; nevertheless, its effector mechanisms may result in immunopathologies and exacerbate clinical symptoms. This review summarizes the role of the immune response against worms, with an emphasis on the Th₂ response, which is a hallmark of helminth infections. We characterize non-immune cells (enteric tuft cells—ETCs) responsible for detecting parasites, as well as the role of hematopoietic-derived cells (macrophages, basophils, eosinophils, neutrophils, innate lymphoid cells group 2—ILC2s, mast cells, T cells, and B cells) in initiating and sustaining the immune response, as well as the functions they play in granulomas. The aim of this paper is to review the existing knowledge regarding the immune response against helminths, to attempt to decipher the interactions between cells engaged in the response, and to indicate the gaps in the current knowledge. Full article

(This article belongs to the Special Issue Molecular Research on Host-Parasite Interactions)

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