Search Results (853)

Background: Effective vaccines are essential to overcome the limitations of livestock immunisation, particularly in low- and middle-income countries (LMICs), where scalable, thermostable, and easy-to-administer solutions are needed. Nanoparticle-based delivery systems, such as the Spontaneous Nanoliposome Antigen Particle (SNAP) technology using CoPoP liposomes, offer a promising alternative for subunit vaccine development, although their performance in large animal species remains poorly characterised. CoPoP enables the rapid non-covalent multimeric display of His-tagged protein antigens combined with immunomodulators on liposomes incorporating cobalt porphyrin–phospholipid (CoPoP). Objective: To evaluate the immunogenicity of CoPoP-based liposomes delivering the Theileria parva p67C antigen in cattle and compare their performance in murine models. Methods: Cattle and mice were immunised with p67C formulated in CoPoP liposomes incorporating QS-21 and/or PHAD immunomodulators. Humoral and cellular responses were assessed. Parallel in vitro stimulation of bovine PBMC with Quil-A was used to investigate the mechanistic effects of saponins on bovine cells. Results: CoPoP liposome formulations did not improve p67C immunogenicity in cattle, with antibody responses at least two-fold lower than previously reported results and no detectable cellular responses. In contrast, the same platform induced up to 2000-fold higher antibody titres in mice. This disparity is likely driven by differences in antigen dose relative to body mass, tissue architecture, lymphatic accessibility, and innate immune signalling differences. PHAD-mediated TLR4 activation appeared less effective in cattle, whereas QS-21 induced a broader immune activation, likely through conserved inflammasome pathways. Despite limited immunogenicity, antigen presentation by CoPoP liposomes was preserved. Conclusions: SNAP-based CoPoP liposomes showed strong immunogenicity in mice but limited efficacy in cattle, highlighting the challenges of cross-species translation. Optimisation of antigen dose and adjuvant selection for the targeted species is required, with QS-21 representing a more promising candidate than the TLR4 agonist. The scalability and versatility of SNAP technology support its continued development for multivalent livestock vaccines. Full article

Blepharipa tibialis (Diptera: Tachinidae) is a typical parasitoid fly. It spends most of its lifespan inside its host (Antheraea pernyi larvae) and relies heavily on host nutrition for survival. Whether the gut bacteria characteristics of B. tibialis larvae are associated with host development during the parasitoid process remains unclear. In this study, we used high-throughput sequencing to conduct the first systematic investigation of the gut bacteria of a parasitoid fly, comprehensively revealing the composition, structure, diversity, specificity, and potential functions in B. tibialis larvae parasitizing different host developmental stages. Results show that B. tibialis larval gut bacterial species were highly abundant, with a total of 24 phyla, 41 classes, 84 orders, 127 families, and 194 genera annotated. Although the number of bacterial species in B. tibialis larvae parasitizing different host stages (3rd, 4th, and 5th instar) differed significantly, the community structures were similar, suggesting that host physiological changes and dynamic alterations in the internal microenvironment may drive changes in the larval gut bacteria. Different host developmental stages may alter the gut bacterial composition of B. tibialis larvae, but bacterial functional stability is largely maintained. PICRUSt2 functional prediction indicated that the gut bacterial community may play an important role during the parasitoid process of B. tibialis larvae. This study provides an important basis for research on gut bacteria in tachinid flies (Diptera), supplements gut microbiota data for this group, and offers references for exploring the interaction mechanisms of gut microbiota in parasitoid systems, as well as for developing green control strategies against A. pernyi pests. Full article

Vairimorpha ceranae (formerly Nosema ceranae) is an obligate intracellular parasite that poses a major threat to the health of the honey bee. Circular RNAs (circRNAs) have been recognized as key regulators in gene expression and pathogen–host interactions. However, their expression patterns and regulatory roles in V. ceranae infection remain largely unexplored. In this study, we performed circRNA profiling in V. ceranae spores (NcCK) and the midguts of Apis mellifera ligustica workers at 7 d post inoculation (dpi) and 10 dpi (Nc7T and Nc10T) based on transcriptome sequencing, followed by in-depth investigation of the regulatory roles of differentially expressed circRNAs (DEcircRNAs). In total, 243 circRNAs were identified in V. ceranae, with lengths predominantly ranging from 201 to 400 nucleotides. Comparative analysis screened 70 and 192 DEcircRNAs in the NcCK vs. Nc7T and NcCK vs. Nc10T comparison groups, respectively, with a significant majority being downregulated. The parental genes of these DEcircRNAs were significantly enriched in fundamental cellular processes and critical pathways such as protein processing in the endoplasmic reticulum and ribosome biogenesis. Additionally, we constructed a competing endogenous RNA network, suggesting that DEcircRNAs could potentially interact with DEmiRNAs to modulate mRNAs associated with fungal proliferation-relevant signaling pathways like MAPK, PI3K–Akt, and cAMP. Moreover, numerous DEcircRNAs were predicted to contain internal ribosome entry site elements, indicative of their potential for protein coding. The back-splicing junctions and expression trends of selected DEcircRNAs were successfully validated by RT-PCR and qRT-PCR. Our data not only offer a valuable resource for future functional studies but also provide a basis for elucidating the circRNA-mediated mechanisms underlying microsporidian pathogenesis and host–pathogen interactions. Full article

Gastric nematodes can cause severe diarrheal diseases of waterfowl and threaten waterfowl health and productivity. The immune response mechanism of the host against this parasite is unclear. We investigated the transcriptomic changes, immune related pathways and adaptive molecular responses in infected ducks. RNA sequencing of the gastric tissues of infected and control ducks was followed by differential expression using DESeq2, and functional enrichment and protein–protein interaction networks were constructed. There were 1983 differentially expressed genes (DEGs), including 1317 upregulated genes and 666 downregulated genes. GO and KEGG analyses showed considerable enrichment in immune response, extracellular matrix organization, and chemotaxis and cytokine-mediated signaling pathways, suggesting systemic immune activation and tissue remodeling. The protein–protein interaction network indicated several hub genes that might be central to host defense. Validation by RT-qPCR showed consistent expression trends for some DEGs. These results systematically outline the transcriptomic landscape of ducks infected with Eustrongylides tubifex, offering new insights into host–parasite interactions and immune modulation. The results enhance our understanding of anti-helminth immunity in waterfowl and may inform strategies for disease control in poultry production. Full article

Background: Neglected diseases caused by protozoan parasites remain a major public health burden, particularly in low- and middle-income countries. Among the chemical motifs explored in antiparasitic drug discovery, guanidine-containing compounds have attracted considerable attention due to their strong cationic character, high capacity for hydrogen bonding, and versatility in interacting with biological targets. Methodology: This review summarizes advances reported in the last decade regarding guanidine derivatives with activity against pathogens associated with Chagas disease, human African trypanosomiasis, Leishmaniasis, tuberculosis, toxoplasmosis, dengue and schistosomiasis. Results: Evidence gathered from synthetic, natural, and drug-repurposing studies indicates that the guanidine, guanidine-containing and guanidine-related compounds contribute to modulating biological activity by changing electrostatic interactions, hydrogen-bonding networks, and physicochemical properties, with enzymes, nucleic acids, and membrane-associated targets essential for parasite survival. Across the analyzed studies, several emerging structure–activity relationship trends were identified, including the contribution of polycationic or dicationic architectures, the influence of halogenated or lipophilic substituents, and the dependence of biological activity on the complete molecular framework, including heterocyclic systems, macrocycles, peptide conjugates, hybrid scaffolds, and repurposed drugs. In addition to direct antiparasitic effects, certain guanidine-containing and guanidine-related compounds demonstrate immunomodulatory or host-protective properties, expanding the therapeutic relevance of this class. Despite promising in vitro results, protonation trapping, efflux pump susceptibility, and pharmacokinetic limitations such as poor oral absorption, high polarity, plasma protein binding and limited membrane permeability remain significant challenges for clinical translation. Nonetheless, the integration of medicinal chemistry, computational modeling, and biological screening continues to accelerate the identification of optimized scaffolds. Conclusions: Overall, guanidine-based compounds constitute a promising scaffold for the development of new therapeutic strategies targeting neglected parasitic diseases, and further structural optimization may enable the emergence of candidates with improved efficacy, selectivity, and drug-like properties. Full article

Characterizing the specific interactions of Leishmania species with different host systems is essential for the development and validation of experimental infection models and for identifying potential therapeutic targets. Leishmania parasites elicit diverse host immune responses that result in different levels of disease severity. Here, we developed a murine model of L. panamensis infection and compared the responses of BALB/c and C57BL/6 mice following intradermal ear inoculation. BALB/c mice developed progressive ulcerative lesions associated with high parasite burden, whereas C57BL/6 mice exhibited a transient edema and maintained low parasite levels detected only at early stages of infection. C57BL/6 mice displayed early production of IL-13, IL-4, and IL-10, followed by delayed IFN-γ secretion. In contrast, BALB/c mice showed a mixed Th1/Th2 response at later stages of infection. Humoral responses also differed between strains, with BALB/c mice developing an early and sustained IgG1-dominated response, while C57BL/6 mice exhibited weak and delayed antibody production. These findings suggest that resistance to L. panamensis infection in C57BL/6 mice is associated with an early and transient Th2/regulatory response accompanied by a weak and delayed antibody production. Full article

The mealworm beetle, Tenebrio molitor, is a coleopteran of importance for both immunological and biotechnological research, and it has even been considered as a potential nutraceutical. In recent years, the study of T. molitor has undergone significant development, including immune response, host–parasite interactions, and physiological approaches. However, to perform this type of study, one of the main obstacles is obtaining sufficient hemolymph and viable hemocytes. Thus, we developed a protocol for adult specimens that enables the collection of up to 300 μL of the hemolymph–anticoagulant buffer mixture per specimen, containing approximately 1.5 × 10⁵ hemocytes, with viability ranging from 85% to 90%. The technique involves a double mesothoracic puncture (DMP) and the use of a modified anticoagulant buffer that prevents hemolymph clotting, enabling continuous extravasation and ensuring high yields. Additionally, the hemocytes recovered with this protocol are intact and can be used for subsequent analysis. The hemolymph obtained using this protocol and its applications will help to better understand the processes involving hemolymph and its components in T. molitor, paving the way for further applications. Full article

Generally, ixodid ticks are important ectoparasites of cattle, including those in smallholder production systems in the Eastern Cape Province, where varying environmental conditions influence their distribution and feeding behaviour. This study investigated ecological variation in tick species composition and attachment site preferences in Bos taurus cattle across coastal and inland areas of the Eastern Cape Province, South Africa. Ticks were collected from cattle of different ages, sexes, breeds, and body condition scores. Sampling was conducted prior to acaricide treatment, and ticks were manually removed from standard predilection sites on each animal. Specimens were preserved in 70% ethanol and later identified morphologically at the Döhne Agricultural Development Institute Laboratory. Data were analysed using generalized linear mixed models with a negative binomial distribution to assess the effects of host and environmental factors on tick burden. Descriptive statistics were used to summarise species composition, while inferential statistics were applied to evaluate differences in infestation levels across host-related and spatial variables. A total of 3250 adult ixodid ticks were collected from cattle. The most prevalent species was Rhipicephalus (Boophilus) decoloratus (39.7%), followed by Rhipicephalus evertsi evertsi (21.0%), Amblyomma hebraeum (17.7%), Hyalomma rufipes (5.8%), Ixodes pilosus (5.8%), Rhipicephalus (Boophilus) microplus (4.5%), R. appendiculatus (3.0%), and R. simus (2.5%). Tick burdens were significantly higher in the coastal zone (85 ± 7.5) than in semi-arid inland areas (62 ± 5.9). Attachment site analysis showed significantly higher infestation levels (p < 0.05) on the udder/scrotum compared to other body regions. This study provides baseline information on tick species composition and attachment site ecology in cattle, contributing to improved understanding of host–parasite interactions and supporting the development of targeted, region-specific tick control strategies. Full article

Invertebrates possess an innate immune system that acts non-specifically against pathogens and is regulated by the circadian clock. Using the host–parasite system, Daphnia magna and its bacterial parasite Pasteuria ramosa, we investigated day–night differences in susceptibility. In an infection experiment where hosts were exposed to spores either during the day or night, infection was slightly higher during daytime exposure and in animals treated with exogenous melatonin. Daphnia exhibited rhythmic expression of five immune genes, with low daytime expression and a pronounced, synchronized peak immediately after the transition from day to night. This timing aligns with the documented increase in daytime susceptibility, which may benefit Pasteuria as encounter rates rise when Daphnia forage in sediment during diel vertical migration. Melatonin exposure altered immune gene expression and increased susceptibility both day and night. Melatonin can act as an immune suppressor and may also influence parasite spore maturation. Disruption of circadian rhythms and melatonin signaling by anthropogenic stressors alters the infection dynamics in this freshwater keystone organism, with consequences for population stability, ecosystem functioning, and the conservation of freshwater biodiversity. Our results spotlight the mechanisms underlying infection risk in host–pathogen systems, highlighting the importance of circadian regulation for disease dynamics in freshwater ecosystems. Full article

Infectious diseases remain a major global health challenge, driven by antimicrobial resistance, pathogen persistence, and the limited integration of mechanistically innovative therapeutic approaches. Emerging evidence indicates that epigenetic regulation is fundamental to host–pathogen interactions, influencing transcriptional programmes associated with virulence, immune evasion, stress adaptation, and phenotypic plasticity. In organisms such as bacteria, parasites, and intracellular pathogens, including Mycobacterium tuberculosis and Plasmodium falciparum, chromatin-associated regulators and DNA-modifying enzymes have been identified as dosage-sensitive determinants of infection outcomes. Traditional strategies focus primarily on occupancy-driven enzymatic inhibition. In contrast, targeted protein degradation (TPD) introduces an event-driven pharmacological paradigm in which transient ligand engagement triggers sustained depletion of regulatory proteins. Platforms such as proteolysis-targeting chimeras (PROTACs) and BacPROTACs exemplify the ability to exploit host and pathogen proteolytic systems, thereby expanding the druggable proteome beyond conventional small-molecule targets. This review examines the relationship between epigenetic regulation and pathogen survival, highlights recent advances in degradation technologies, and discusses conceptual and translational challenges in implementing TPD in antimicrobial and antiparasitic drug discovery. Full article

Heme metabolism is central to the biology of malaria parasites and to the mechanism of action of artemisinin-based therapies. Within malaria-infected red blood cells (RBCs), heme-related chemistry arises from multiple nested metabolic sources that function as “Russian dolls”: the truncated heme biosynthetic capacity of the host erythrocyte, the parasite’s own heme synthesis pathway, and host heme released through hemoglobin digestion in the parasite food vacuole. These overlapping metabolic layers create distinct pools of heme that can influence redox balance and drug activation. Recent studies highlight that exogenous 5-aminolevulinic acid (5-ALA) can perturb host heme biosynthesis in infected erythrocytes, potentially increasing intracellular levels of the heme intermediate protoporphyrin IX and sensitizing parasites to oxidative stress. However, the extent to which such metabolic perturbations affect artemisinin susceptibility depends strongly on parasite stage and exposure duration. Here we review the compartmentalized architecture of heme metabolism in malaria-infected RBCs and discuss how these nested vulnerabilities may be exploited for therapeutic intervention. Full article

Toxoplasma gondii, an obligate intracellular protozoan infecting approximately one-third of the global population, poses a significant yet underappreciated threat to reproductive health in both sexes. Although this parasite has long been linked to birth defects caused by infection during pregnancy, new research shows that it also reduces fertility in both sexes through different but related mechanisms. This review synthesizes knowledge on T. gondii-induced reproductive pathology across females and males, examining shared mechanistic themes while respecting tissue-specific differences, and evaluates emerging therapeutic strategies. In females, the parasite establishes persistent uterine reservoirs, triggers decidual immune dysregulation characterized by NK cell cytotoxicity, M1 macrophage polarization, Treg apoptosis, and inflammasome-mediated pyroptosis, while disrupting estrogen and progesterone signaling through both host receptor modulation and intrinsic parasite steroidogenic enzymes (TgCYP450mt, TgMAPR, Tg-HSD). In males, T. gondii breaches the blood–testis barrier, induces germ cell and Leydig cell apoptosis via ER stress and caspase pathways, impairs sperm quality parameters across acute and chronic infection, and disrupts the hypothalamic–pituitary–gonadal axis. Conserved molecular mechanisms—including NLRP3 inflammasome activation, PERK/eIF2α/ATF4/CHOP-mediated ER stress, and oxidative stress—operate in both reproductive tissues. The parasite’s intrinsic steroidogenic capability and bidirectional hormonal manipulation represent a paradigm shift in understanding host–parasite interactions. Conventional antiparasitics face limitations due to poor reproductive sanctuary penetration. Immunomodulatory approaches targeting Trem2, Tim-3, and the NLRP3 inflammasome show promise, along with natural products including Inonotus obliquus polysaccharide and ginseng polysaccharide. Nanomedicine platforms and mRNA vaccine candidates offer new directions for overcoming tissue barrier limitations. Toxoplasma gondii represents a fundamental threat to fertility and pregnancy outcomes rather than merely a risk for congenital infection. Integrated therapeutic strategies addressing direct parasitism, immunopathology, and endocrine disruption are needed. Longitudinal cohort studies, strain-specific mechanistic comparisons, and clinical trials of immunomodulatory adjuncts are urgently required. Full article

Chicken coccidiosis, a severe intestinal parasitic disease caused by Eimeria protozoa, causes substantial annual economic losses to the global poultry industry. This study focused on investigating the role of tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6) in modulating chicken innate immune responses against Eimeria tenella (E. tenella) infections. Here, we show that TRAF6 is sensitive to the process of E. tenella infection, and cecal tissue responds to the early infection of E. tenella by up-regulating the expression of TRAF6. Specifically, TRAF6 overexpression enhances E. tenella-induced activation of the NF-κB pathway (a core innate immune signaling cascade), thereby promoting host inflammatory cytokines production and cell apoptosis, while TRAF6 knockdown mitigates these pathological effects. Mechanistically, TRAF6-mediated regulation of NF-κB pathway activation and inflammatory responses during E. tenella infection can be specifically targeted by key microRNAs (miRNA), gga-miR-7b, in chickens. Taken together, this study identifies that TRAF6 plays an important regulatory role in innate immune response against E. tenella infection, providing novel insights into host–parasite interactions and potential targets for coccidiosis control. Full article

The circulatory system of cuttlefish (family Sepiidae) has been extensively studied; however, a comprehensive anatomical reconstruction of bobtail squids (family Sepiolidae) remains limited despite their ecological and evolutionary importance within Decapodiformes. This study reconstructs the circulatory architecture of sepiolids through comparative histological analysis and documents microorganisms or parasites associated with renal tissues. Two bobtail squid species, Rossia bipapillata and Sepiolina nipponensis, were examined using serial histological sections, while four cuttlefish species—Sepia lycidas, Sepia esculenta, Sepia japonica, and Sepia tenuipes—were analyzed for comparative purposes. Morphometric parameters, including sex, total length, and mantle length, were recorded prior to histological processing. Branchial hearts and renal appendages were sectioned using serial microtomy (~120 sections per specimen) and stained with hematoxylin and eosin, periodic acid–Schiff, Masson’s trichrome, and Giemsa to visualize vascular continuity and tissue organization. Histological observations confirmed vascular connections between the gills, branchial hearts, the systemic heart, and renal appendages, enabling reconstruction of the sepiolid circulatory pathway. In addition, the light organ characteristic of Sepiolidae was identified as a tissue receiving oxygenated blood within the circulatory network. Renal tissues revealed the presence of parasitic organisms, including Dicyema in cuttlefish and ciliates of the genus Chromidina in bobtail squids. Morphological observations revealed structural diversity in Chromidina, including characteristic spiral anterior features and variation in body form, as well as developmental variation in nuclear number relative to body length in dicyemids. These findings provide new insights into cephalopod circulatory organization, parasite diversity, and host–parasite interactions. Full article

Leeches (Hirudinea) are ecologically important annelids that interact with a wide range of aquatic vertebrates, yet their diversity, distribution, and epidemiological relevance remain poorly documented in North Africa. Here, we provide a comprehensive synthesis of freshwater and marine leech species reported from the Maghreb (Algeria, Tunisia, and Morocco), based on an extensive review of the available literature. In total, 21 species belonging to 13 genera and four families (Glossiphoniidae, Erpobdellidae, Hirudinidae, and Piscicolidae) are documented, with updated information on their ecology, host associations, and geographic distribution. In addition to this regional checklist, we report the first confirmed case of Batracobdella algira heavy parasitism on the Berber toad (Sclerophrys mauritanica) in Algeria. A single adult toad was found heavily infested by multiple leeches (n = 17), some of which bore spermatophores attached near the reproductive opercula, suggesting possible in situ mating behavior on the host. The high infestation observed in this single specimen may constitute an outlier, requiring further sampling to assess the effect of leeches on the anuran population in the region. By integrating faunistic data with a novel field observation, this study highlights the overlooked leech biodiversity in the Maghreb and suggests their possible ecological and epidemiological significance. Our findings emphasize the need for further investigations into leech–host interactions, pathogen carriage, and their implications for amphibian conservation and One Health in North Africa. Full article