Submit to Special Issue Submit Abstract to Special Issue Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Investigating Host-Parasite Interactions for the Discovery of Novel Therapies and Vaccine Targets

Special Issue Editors
Special Issue Information
Keywords
Benefits of Publishing in a Special Issue
Published Papers

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

Deadline for manuscript submissions: 20 January 2026 | Viewed by 7915

Share This Special Issue

Special Issue Editor

Dr. Natalie Nieuwenhuizen

E-Mail Website
Guest Editor

Institute for Hygiene and Microbiology, Julius-Maximilians-Universität Würzburg, Josef-Schneider-Str. 2, 97080 Würzburg, Germany
Interests: infectious disease; immunology; host-pathogen interactions; tuberculosis; vaccines; fungal infection; leishmaniasis; helminth infection; IL-4 receptor alpha; TGF-beta; activin A
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Parasite infections are a significant global health problem, affecting millions of people worldwide, particularly in sub-tropical and tropical regions and in communities with limited access to clean water and sanitation. Helminths (e.g., Schistosoma, Ascaris, Trichuris), unicellular eukaryotes (e.g. Plasmodium, Leishmania, Trypanosoma), protozoans (e.g., Toxoplasma) and athropods (e.g., mosquitoes, ticks) represent diverse groups of organisms that can cause a wide range of diseases, from mild to life-threatening. On the World Health Organization’s list of top 20 priority neglected tropical diseases, 12/20 are caused by parasites.

Understanding the intricate molecular interactions between hosts and parasites is crucial for the development of novel therapies and vaccine targets. Parasites are in a dependent relationship with their hosts and have evolved mechanisms to avoid or suppress host immune responses over millions of years.

This Special Issue aims to highlight recent advancements in the field of host–parasite interactions, with a particular focus on molecular studies that could inform the development of novel drug and vaccine targets. We are particularly interested in research articles, but reviews will also be considered if they have something new to contribute to the field. We invite contributions from researchers working on a diverse range of host-parasite systems, including but not limited to, the following:

Soil-transmitted helminths;
Schistosomiasis;
Malaria;
Leishmaniasis;
Trypanosomiasis;
Echinococcus;
Anisakiasis.

Dr. Natalie Nieuwenhuizen
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

parasites
host-pathogen interactions
helminths
worms
protozoans
leishmania
malaria
schistosomiasis
trypanosomiasis
ascariasis
anisakiasis
vectors
mosquitoes
ticks
neglected tropical diseases

Benefits of Publishing in a Special Issue

Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
Reprint: MDPI Books provides the opportunity to republish successful Special Issues in book format, both online and in print.

Further information on MDPI's Special Issue policies can be found here.

Published Papers (6 papers)

Download All Papers

Order results

Result details

Show export options Show export options

Select all

Export citation of selected articles as:

Research

Jump to: Review

25 pages, 5050 KB

Open AccessArticle

Catalytically Active Recombinant Cysteine Proteases of Haemonchus contortus: Their Ability to Degrade Host Blood Proteins and Modulate Coagulation

by Athira C. Karunakaran, Mariam Bakshi, Arunraj M. Rajendrakumar, Jennifer H. Wilson-Welder, Raffi V. Aroian, Erich M. Schwarz, E. Jane Homan, Gary R. Ostroff, Ethiopia Beshah, Eliseo Miramontes, Marianne Dias Papadopoulos, Scott A. Bowdridge, Dante S. Zarlenga, Xiaoping Zhu and Wenbin Tuo

Int. J. Mol. Sci. 2025, 26(24), 12077; https://doi.org/10.3390/ijms262412077 - 16 Dec 2025

Viewed by 192

Abstract

Haemonchus contortus is a blood-feeding gastrointestinal nematode that significantly impacts the health and productivity of small ruminants. The burden of parasitism and the escalating incidence of anthelmintic resistance necessitate alternative control methods. Here, we characterize the enzymatic activities of five mammalian cell-expressed recombinant H. contortus cysteine proteases (HcCPs), which include two cathepsin B-like proteins (HcCBP1 and HcCBP2) and three cysteine protease 1 proteins (HcCP1a, HcCP1b, and HcCP1c). We hypothesize that these enzymes degrade host blood proteins, thereby facilitating the parasite’s nutrient acquisition and survival. Using synthetic cathepsin (cat) substrates, we show that HcCBP2 was the only protein that exhibited high catB/L but low catB or catK activity, which was inhibited by the cysteine protease inhibitor E-64. All mHcCPs degraded fibrinogen (Fg), which led to delayed plasma clotting, reduced clot density, and lysed plasma clots. All HcCPs partially degraded hemoglobin (Hb), except for mHcCBP2, which degraded Hb and bovine serum albumin completely and bovine IgG partially in the presence of a reducing agent. In conclusion, by sustaining blood feeding and facilitating immune evasion and nutrient acquisition, the HcCPs may play an essential role in the parasite’s survival. Thus, vaccines or cysteine protease inhibitors targeting these parasitic enzymes may mitigate or prevent infections. Full article

(This article belongs to the Special Issue Investigating Host-Parasite Interactions for the Discovery of Novel Therapies and Vaccine Targets)

► Show Figures

Figure 1

20 pages, 2221 KB

Open AccessArticle

Thioester-Containing Protein TEP27 in Culex quinquefasciatus Promotes JEV Infection by Modulating Host Immune Function

by Yutian Huang, Yuwei Liu, Rongrong Li, Xi Zhu, Ruidong Li, Sihao Peng, Xin An, Yuxin Yang, Yuanyuan Liu, Yiping Wen, Qin Zhao, Shan Zhao, Fei Zhao, Rui Wu, Xiaobo Huang, Qigui Yan, Yifei Lang, Yiping Wang, Yajie Hu, Yi Zheng, Sanjie Cao and Senyan Du Show full author list Hide full author list

Int. J. Mol. Sci. 2025, 26(23), 11727; https://doi.org/10.3390/ijms262311727 - 3 Dec 2025

Viewed by 243

Abstract

Thioester-containing proteins (TEPs), which are distinguished by the thioester motif (GCGEQ), are essential to arthropods’ defense against infections. Although TEPs have been extensively investigated in Anopheles, Aedes, and Drosophila, their functions in Culex mosquitoes remain inadequately explored. Interestingly, we discovered that Culex TEPs exhibit functional antagonism to their orthologs in other species, actively facilitating viral infection in this vector. In this study, we identified nine TEP genes in Culex quinquefasciatus, three of which were found to critically facilitate Japanese encephalitis virus (JEV) infection, with CqTEP27 exhibiting the most pronounced proviral effect. Mechanistically, CqTEP27 may have suppressed the production of several antimicrobial peptides (AMPs), which increased JEV replication. Our work also highlights the potential of targeting susceptibility factors such as CqTEP27 to block pathogen acquisition. Notably, the rate of mosquito infection was significantly decreased by membrane blood feeding antisera against CqTEP27. Therefore, vaccination against CqTEP27 offers a workable method of avoiding JEV infection. According to our research, CqTEP27 is a promising target for the development of vaccines that prevent JEV transmission. By preventing viral infection in mosquitoes that feed on immunized hosts, this approach can directly disrupt the natural transmission cycle, offering a novel strategy to reduce the disease burden. Full article

(This article belongs to the Special Issue Investigating Host-Parasite Interactions for the Discovery of Novel Therapies and Vaccine Targets)

► Show Figures

Graphical abstract

14 pages, 2785 KB

Open AccessArticle

Exploring Fourier-Transform Infrared Microscopy for Scabies Mite Detection in Human Tissue Sections: A Preliminary Technical Feasibility Study

by Maximilian Lammer, Matthias Schmuth, Paul Bellmann, Verena Moosbrugger-Martinz, Bernhard Zelger, Birgit Moser, Roland Stalder, Christian Wolfgang Huck, Miranda Klosterhuber and Johannes Dominikus Pallua

Int. J. Mol. Sci. 2025, 26(23), 11597; https://doi.org/10.3390/ijms262311597 - 29 Nov 2025

Viewed by 306

Abstract

Scabies, caused by Sarcoptes scabiei var. hominis, remains difficult to diagnose in histological routine when mite fragments are sparse or degraded. We explored whether Fourier-transform infrared (FTIR) microscopy can detect chitin-associated spectral signatures of scabies mites in formalin-fixed paraffin-embedded (FFPE) human skin sections and distinguish them from surrounding host tissue. FFPE sections from six patients with histologically confirmed crusted scabies were analysed by FTIR imaging, univariate mapping of selected bands, and multivariate image analysis within the 1000–1200 cm⁻¹ carbohydrate region. Spectra from mite exoskeleton, stratum corneum, and dermis were compared, and absorbance at 1072 cm⁻¹ was quantified across all samples. Mite regions showed consistently higher 1072 cm⁻¹ absorbance than adjacent epidermal and dermal compartments, and unsupervised clustering reproducibly delineated mite-associated domains that co-localised with structures identified on haematoxylin-and-eosin-stained sections. Within this small, preliminary proof-of-concept cohort and in the absence of healthy or disease controls, the data do not allow estimation of clinical diagnostic performance at the patient level, but demonstrate the technical feasibility and analytical robustness of FTIR microscopy for intra-lesional detection of chitin-rich parasite structures in scabies lesions and provide a framework for future comparative studies in larger, prospectively collected cohorts. Full article

(This article belongs to the Special Issue Investigating Host-Parasite Interactions for the Discovery of Novel Therapies and Vaccine Targets)

► Show Figures

Graphical abstract

17 pages, 2807 KB

Open AccessArticle

Genome-Wide Inference of Essential Genes in Dirofilaria immitis Using Machine Learning

by Túlio L. Campos, Pasi K. Korhonen, Neil D. Young, Sunita B. Sumanam, Whitney Bullard, John M. Harrington, Jiangning Song, Bill C. H. Chang, Richard J. Marhöfer, Paul M. Selzer and Robin B. Gasser

Int. J. Mol. Sci. 2025, 26(20), 9923; https://doi.org/10.3390/ijms26209923 - 12 Oct 2025

Cited by 1 | Viewed by 660

Abstract

The filarioid nematode Dirofilaria immitis is the causative agent of heartworm disease, a major parasitic infection of canids, felids and occasionally humans. Current prevention relies on macrocyclic lactone-based chemoprophylaxis, but the emergence of drug resistance highlights the need for new intervention strategies. Here, we applied a machine learning (ML)-based framework to predict and prioritise essential genes in D. immitis in silico, using genomic, transcriptomic and functional datasets from the model organisms Caenorhabditis elegans and Drosophila melanogaster. With a curated set of 26 predictive features, we trained and evaluated multiple ML models and, using a defined threshold, we predicted 406 ‘high-priority’ essential genes. These genes showed strong transcriptional activity across developmental stages and were inferred to be enriched in pathways related to ribosome biogenesis, translation, RNA processing and signalling, underscoring their potential as anthelmintic targets. Transcriptomic analyses suggested that these genes are associated with key reproductive and neural tissues, while chromosomal mapping revealed a relatively even genomic distribution, in contrast to patterns observed in C. elegans and Dr. melanogaster. In addition, initial evidence suggested structural variation in the X chromosome compared with a recently published D. immitis assembly, indicating the importance of integrating long-read sequencing with high-throughput chromosome conformation capture (Hi-C) mapping. Overall, this study reinforces the potential of ML-guided approaches for essential gene discovery in parasitic nematodes and provides a foundation for downstream validation and therapeutic target development. Full article

(This article belongs to the Special Issue Investigating Host-Parasite Interactions for the Discovery of Novel Therapies and Vaccine Targets)

► Show Figures

Figure 1

17 pages, 3029 KB

Open AccessArticle

Evaluation of Serum Supplementation on the Development of Haemonchus contortus Larvae In Vitro and on Compound Screening Results

by Sandani S. Thilakarathne, Aya C. Taki, Tao Wang, Cameron Nowell, Bill C. H. Chang and Robin B. Gasser

Int. J. Mol. Sci. 2025, 26(3), 1118; https://doi.org/10.3390/ijms26031118 - 28 Jan 2025

Cited by 2 | Viewed by 3765

Abstract

A high-throughput platform for assessing the activity of synthetic or natural compounds on the motility and development of Haemonchus contortus larvae has been established for identifying new anthelmintic compounds active against strongylid nematodes. This study evaluated the impact of serum supplementation on larval development, motility and survival in vitro and its implications for phenotypic compound screening. Of five blood components assessed, 7.5% sheep serum significantly enhanced larval development, motility and survival compared to the original medium (LB*), leading to the formulation of an improved medium (LBS*). Proteomic analysis revealed marked differences in protein expression in larvae cultured in LBS* versus LB*, including molecules associated with structural integrity and metabolic processes. The phenotypic screening of 240 compounds (“Global Priority Box” from Medicines Malaria Venture) using LBS* yielded results distinct from those in LB*, highlighting the effect of culture conditions on screening assessments. These findings indicate/emphasise the critical need to evaluate and optimise culture media for physiologically relevant conditions in screening platforms, improving the reliability of anthelmintic discovery. Full article

(This article belongs to the Special Issue Investigating Host-Parasite Interactions for the Discovery of Novel Therapies and Vaccine Targets)

► Show Figures

Figure 1

Review

Jump to: Research

22 pages, 2214 KB

Open AccessReview

Extracellular Vesicles Derived from Trypanosomatids: The Key to Decoding Host–Parasite Communication

by Armanda Rodrigues, Juliana Inês Weber, João Durães-Oliveira, Cláudia Moreno, Micheli Ferla, Maria de Aires Pereira, Ana Valério-Bolas, Bruna Eugênia de Freitas, Telmo Nunes, Wilson T. Antunes, Graça Alexandre-Pires, Isabel Pereira da Fonseca and Gabriela M. Santos-Gomes

Int. J. Mol. Sci. 2025, 26(9), 4302; https://doi.org/10.3390/ijms26094302 - 1 May 2025

Cited by 1 | Viewed by 2082

Abstract

Trypanosomatids constitute a family of parasitic protozoa that cause significant human and veterinary diseases that are classified as neglected zoonotic diseases (NZDs). In a rapidly evolving world, these diseases have the potential to become a world health problem no longer solely associated with low-income countries. Therefore, the development of new strategies to control and restrain the dissemination of trypanosomatids is imperative. Extracellular vesicles (EVs) are a heterogeneous group of membrane-enclosed vesicles released by prokaryotic and eukaryotic cells. They can be found in diverse body fluids that carry biologically active molecules, including proteins, nucleic acids, lipids, and carbohydrates. EVs participate in cell-to-cell communication by delivering their cargo content to recipient cells. Thus, EVs play a role in regulating normal physiological processes, including immune surveillance and tissue repair, as well as being involved in pathological conditions, like cancer. In recent years, EVs have attracted significant attention from the scientific community, mainly due to their immune regulatory properties. Therefore, this review examines the role played by trypanosomatid-derived EVs in leishmaniases and trypanosomiasis, highlighting their biological role in host–parasite communication and exploring their potential future applications in controlling NZDs, especially those caused by trypanosomatids. Full article

(This article belongs to the Special Issue Investigating Host-Parasite Interactions for the Discovery of Novel Therapies and Vaccine Targets)

► Show Figures

Journal Menu

Journal Browser

Investigating Host-Parasite Interactions for the Discovery of Novel Therapies and Vaccine Targets

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Published Papers (6 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI