Search Results (565)

Background/Objectives: Perioperative fasting combined with procedure-related trauma increases the risk of malnutrition and determines the treatment outcomes of surgical patients. The aim of this study was to assess the range of metabolic deficiencies and the effectiveness of oral nutritional supplements (ONSs) after surgical intervention. Methods: 84 patients undergoing elective abdominal surgery were included in this study. Patients were divided into three groups: receiving a low-osmotic ONS (Group I), high-osmotic ONS (Group II), and Group III, who did not receive any oral supplementation. The clinical assessment involved body weight measurements and metabolic blood tests preoperatively and on the 4th, 7th, 14th, and 28th postoperative days. Results: The mean blood levels of total protein, albumin, cholesterol, and blood lymphocyte count decreased in the first 4 days after surgery and returned to baseline between 7 and 14 days. Similarly, BMI dropped during the first two weeks and then stabilized or returned to pre-surgery values. Triglycerides initially increased and, after 14 days, started to normalize. Patients receiving an ONS compensated quicker than the control group and more efficiently with low-osmotic supplements. Conclusions: Surgical trauma is associated with metabolic deficiency. The early administration of ONSs provides significant benefits to patients undergoing abdominal surgery. Low-osmotic supplements are especially recommended due to better tolerance. Full article

Background/Objectives: Tuberculosis, caused by Mycobacterium tuberculosis, remains a major global health challenge requiring novel prevention strategies. This study aims to developed an immunoinformatics-guided framework coupled with experimental screening to prioritize for multi-epitope mRNA vaccine design. Methods: Eight immunologically relevant antigens were computationally analyzed to predict cytotoxic (CTL) epitopes and helper T lymphocyte (HTL) epitopes. Population coverage, immune simulation, molecular docking, and normal mode analysis (NMA) were performed in silico. To evaluate peptide immunoreactivity, human IFN-γELISPOT assays were conducted using the candidate peptides, though HLA restriction was not experimentally validated. Results: The workflow identified 14 candidate CTL and 8 HTL epitopes, yielding an estimated global population coverage of 82.6% (60.7% in China; 51.2% in Indonesia). Immune simulations predicted robust humoral and Th1-associated cellular responses, though sustained CD8⁺ memory responses appeared limited. Docking and NMA suggested favorable structural interactions with TLR3 and TLR4. Crucially, the IFN-γ ELISPOT assay validated eight reactive epitopes that partially coincided with computational predictions within the tested donor group. Conclusions: This study establishes an integrated computational–experimental workflow for T cell epitope prioritization. The identified reactive epitopes provide a preliminary immunological basis and candidate pool for the future design and evaluation of multi-epitope mRNA vaccine strategies against tuberculosis. Full article

Background/Objectives: Childhood obesity is associated with chronic low-grade systemic inflammation. This exploratory cross-sectional study aimed to evaluate associations between a comprehensive panel of serum micronutrient levels and four systemic inflammatory indices—neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and monocyte-to-lymphocyte ratio (MLR)—in a pediatric cohort, with iron as the primary focus and zinc as a secondary exploratory analysis. Methods: We included 410 children (mean age 7.2 ± 3.8 years; 205 male) attending a tertiary pediatric clinic. Of these, 399 had complete BMI percentile data and were included in obesity-stratified analyses; patients were classified as having obesity (BMI ≥ 95th percentile; n = 56) or not having obesity (n = 343). The remaining 11 children lacked BMI percentile data and were included only in full-cohort analyses. Serum iron, ferritin, folate, zinc, vitamin D, vitamin B12, magnesium, and phosphorus were measured alongside complete blood count parameters. Spearman correlations and multivariable ordinary least squares regression were performed. Benjamini–Hochberg false discovery rate (FDR)-adjusted q-values were computed for all Spearman correlations; all remaining analyses are exploratory and all findings should be interpreted with caution. Results: All four inflammatory indices were significantly higher in children with obesity (SII: 487.1 vs. 332.1, p < 0.001; NLR: 1.30 vs. 1.03, p = 0.001). Low serum iron was more prevalent in the group with obesity (42.9% vs. 27.1%, p = 0.025). In multivariable regression, serum iron was significantly associated with NLR (β = −0.009, 95% CI [−0.012, −0.005], p < 0.001) and SII (β = −3.268, 95% CI [−4.404, −2.132], p < 0.001) after adjustment for age and BMI percentile. In an exploratory analysis restricted to children with obesity and complete data (n = 39), zinc was associated with SII (β = −11.912, 95% CI [−21.836, −1.988], p = 0.025); however, the overall model was non-significant (p = 0.067), zinc showed no association in the full cohort, and—given the small sample and absence of multiple comparison correction—this finding must be considered strictly hypothesis-generating. Conclusions: Systemic inflammatory burden is elevated in children with obesity. Iron shows consistent associations with inflammatory indices independent of age and BMI. Zinc shows a potentially relevant, exploratory association with inflammation, specifically in the subgroup with obesity, warranting replication in adequately powered prospective studies. These findings are consistent with a role for iron status assessment in the clinical evaluation of pediatric obesity and warrant further prospective investigation of zinc-related inflammatory associations. Full article

Bone loss in the maxillofacial region arises from multiple causes, including periodontal disease, trauma, surgical procedures, infection, congenital anomalies, and cancer. Traditional treatment relies on bone grafting, either alone or in combination with biomaterials. Advances in tissue engineering have introduced synthetic or natural scaffolds to mimic the mineralized bone matrix. Natural scaffolds offer excellent biocompatibility and similarity to native tissue but often lack sufficient mechanical strength and exhibit poor degradation rates. Synthetic scaffolds provide tunable porosity and mechanical stability; however, their biological inertness makes them poor sources of osteogenic signaling. A key factor in the success of any scaffold is its interaction with the host immune system. Upon implantation, the innate immune response is initiated, with neutrophils and macrophages being the first cells to contact the scaffold. Macrophage polarization toward proinflammatory (M1) or anti-inflammatory (M2) phenotypes determines whether the microenvironment favors inflammation or remodeling. The adaptive immune response also plays a critical role: T and B lymphocytes may promote tolerance and integration through Th2/Treg pathways and antibody-mediated regulation, or they may trigger chronic inflammation and rejection through Th1/Th17 activation. This review examines the natural and synthetic materials used for bone remodeling and their biological properties. It then outlines the sequence of immune events occurring from the moment a scaffold is implanted to its potential integration or failure. Finally, this study highlights the relevance of cellular models and in vitro assays for the early evaluation of immunogenicity and biocompatibility, which are essential for optimizing scaffold design and improving outcomes in maxillofacial bone regeneration. Full article

Kidney transplantation remains the optimal treatment for end-stage renal disease, yet long-term allograft survival has plateaued due to persistent rejection. This review provides a comprehensive overview of the inflammatory and immune pathways implicated in kidney allograft rejection, integrating current evidence from basic and translational research. Ischemia–reperfusion injury initiates an inflammatory cascade through the release of damage-associated molecular patterns, activating Toll-like receptors and the complement system, thereby priming the alloimmune response. Innate immune cells, including macrophages, dendritic cells, and natural killer cells, bridge sterile tissue injury to adaptive alloimmunity, while the emerging concept of trained immunity reveals long-lasting epigenetic reprogramming of monocytes with direct implications for graft longevity. The adaptive response encompasses T cell-mediated rejection, driven by Th1, Th17, and CD8⁺ cytotoxic lymphocytes, and antibody-mediated rejection, mediated by donor-specific antibodies through complement activation and antibody-dependent cellular cytotoxicity. Key signalling pathways, including JAK-STAT, NF-κB, NLRP3 inflammasome, and mTOR, amplify allograft inflammation and promote progression toward chronic injury. Macrophage polarisation and macrophage-to-myofibroblast transition have been identified as major drivers of interstitial fibrosis and late graft failure. Recent advances in non-invasive biomarkers, such as donor-derived cell-free DNA and molecular phenotyping, are transforming rejection diagnostics. Emerging therapies, including costimulation blockade, anti-CD38 antibodies, complement inhibitors, and regulatory T cell-based approaches, offer the potential to shift transplant medicine toward precision-guided, tolerance-inducing strategies. This review synthesises these developments and discusses future perspectives for improving long-term allograft outcomes. Full article

This translational synthesis highlights the potential role of obesity-induced low-grade chronic inflammation in modulating clinical outcomes among patients with spondyloarthritis (SpA). Obesity transforms adipose tissue into a pro-inflammatory endocrine organ, where hypertrophic adipocytes release adipokines such as leptin alongside cytokines including TNF-α and IL-6, potentially contributing to macrophage polarization toward an M1 phenotype and activating NF-κB signaling pathways. This systemic immunometabolic priming may lower activation thresholds at the enthesis—the primary pathological site in SpA—potentially amplifying IL-23/IL-17 axis activity via Th17 bias, innate-like lymphocyte responses, and stromal–immune crosstalk under mechanical stress. Clinically, patients with SpA and obesity have been reported to demonstrate heightened disease activity (BASDAI, ASDAS), impaired function (BASFI), accelerated radiographic progression (syndesmophytes, enthesophytes), and diminished biologic response rates, potentially attributable to pharmacokinetic alterations (e.g., subtherapeutic TNF inhibitor levels) and pharmacodynamic resistance. Multisystem comorbidities, including non-alcoholic fatty liver disease, cardiovascular events, metabolic syndrome, sleep disturbances, and depression, further exacerbate morbidity and diminish quality of life. Therapeutic implications emphasize obesity as a modifiable disease modifier. Weight loss interventions, including hypocaloric diets, anti-inflammatory regimens (e.g., Mediterranean diet), multicomponent exercise, GLP-1 receptor agonists, and bariatric surgery, have been associated with reductions in inflammatory biomarkers, improved remission rates (MDA, DAPSA), and prolonged drug survival by restoring adipokine balance and disrupting mechano-inflammatory loops. Future randomized controlled trials should prioritize long-term evaluations of integrated multidisciplinary strategies that combine metabolic optimization with immunomodulatory therapies, addressing adherence challenges through psychological support and patient-tailored protocols, while elucidating dose–response relationships for GLP-1RAs and exercise in diverse SpA subtypes to establish precision management paradigms that mitigate cardiometabolic burden and improve holistic outcomes. Full article

Hematologic malignancies arise and progress within a systemic ecosystem in which the gut microbiota is an increasingly recognized, partially modifiable component. Across acute leukemias, chronic lymphocytic leukemia, plasma cell disorders, lymphomas, and clonal myeloid neoplasms, human studies consistently report reduced microbial diversity, depletion of barrier-supportive, short-chain fatty acid-producing commensals, and enrichment of Gram-negative, pro-inflammatory, or hospital-adapted taxa. These alterations are associated with pre-leukemic clonal expansion, adverse genetic and immunological features, progression from precursor conditions, and inferior outcomes after chemotherapy, immunochemotherapy, chimeric antigen receptor T-cell therapy, and allogeneic hematopoietic stem cell transplantation. Mechanistic work in animal models and ex vivo systems demonstrates that microbiota-derived signals and metabolites—including Th17/IL-17-skewing consortia and the lipopolysaccharide intermediate ADP heptose sensed by the cytosolic receptor ALPK1—can actively modulate hematopoietic stem and progenitor cell fitness, inflammatory circuits, and malignant cell survival, supporting a causal role in disease biology. At the same time, major knowledge gaps remain because most human cohorts are small, single-center, and cross-sectional, frequently rely on 16S rRNA profiling, and are vulnerable to dietary, geographic, and treatment-related confounding. Within this context, three translational domains appear particularly promising: pharmaco-microbiomics, microbiome-informed risk stratification, and rational microbiota-targeted interventions, particularly diet-based strategies and antimicrobial stewardship. Here, we provide an integrated, disease-spanning synthesis of these data, emphasizing clonal hematopoiesis and myeloid neoplasms as emerging examples of microbiota–marrow crosstalk and outlining practical priorities for embedding microbiome science into future hematologic trials. Routine microbiome profiling or empiric microbiota-directed therapies cannot yet be recommended in everyday hematology practice, but integrating microbiome science into prospective therapeutic and transplant trials offers a realistic path to improved disease modeling, biomarker development, and rational adjunctive strategies to enhance outcomes for patients with hematologic malignancies. Full article

Toxoplasma gondii is an obligate intracellular protozoan parasite that causes toxoplasmosis, posing a significant threat to human health and livestock production worldwide. Although monovalent DNA or mRNA vaccines often confer only partial protection, whether these platforms can be effectively integrated into a heterologous prime–boost regimen against T. gondii remains to be fully elucidated. Here, we constructed GRA35-encoding DNA and mRNA vaccines and evaluated their immunogenicity and protective efficacy, administered either alone or in heterologous prime–boost combinations, in C57BL/6 and BALB/c mice. Both vaccines induced strong antigen-specific immune responses, with the heterologous prime–boost regimen eliciting the strongest effects and conferring the most robust and consistent protection across both mouse strains. Immunization triggered a predominantly Th1-skewed response characterized by significantly elevated IFN-γ production, accompanied by balanced antigen-specific IgG responses. Moreover, vaccinated mice developed rapid and potent cytotoxic T lymphocyte (CTL) responses. Following challenge with the RH and PRU strains, vaccinated mice exhibited prolonged survival and significantly reduced brain cyst burdens following PRU challenge compared with control groups. Collectively, these findings indicate that GRA35-based nucleic acid vaccines, particularly when administered in a heterologous prime–boost regimen, elicit multifaceted protective immune responses and represent promising vaccine candidates against T. gondii infection. Full article

Background: Currently marketed hepatitis B vaccines are primarily recombinant protein vaccines. However, their antigen immunogenicity is relatively weak, requiring combination with effective adjuvants to enhance the immune response. The development of novel, highly effective adjuvants is a key strategy for optimizing vaccine performance. Polyinosinic-polycytidylic acid (PolyI:C), a synthetic double-stranded RNA analog, activates TLR3/RLR pathways to enhance T-cell priming and cellular immunity. However, its utility as a sole adjuvant is limited by rapid nuclease degradation and poor cytosolic delivery. Lipid nanoparticles (LNPs), a mature delivery platform, enable high encapsulation efficiency, efficient cellular uptake, and endosomal escape. Objectives: This study aimed to evaluate the adjuvant effect of LNP-encapsulated PolyI:C (LNP-PolyI:C) on the immunogenicity of hepatitis B surface antigen (HBsAg) in vivo. Methods: The colloidal stability of LNP-PolyI:C stored at 2–8 °C for 9 months was monitored using dynamic light scattering (DLS) on a Zetasizer Lab instrument. Serum levels of HBsAg-specific IgG, IgG1, and IgG2a antibodies in immunized Kunming mice were measured by enzyme-linked immunosorbent assay (ELISA). The secretion of HBsAg-specific cytokines by splenocytes was analyzed using flow cytometry and enzyme-linked immunospot (ELISpot) assay. Results: The results demonstrated that the LNP-encapsulated PolyI:C adjuvant significantly increased the secretion of HBsAg-specific IFN-γ, IL-2, and TNF-α by splenocytes, indicating a Th1-biased and cytotoxic T lymphocyte (CTL)-mediated cellular immune response. In addition, this formulation markedly elevated serum titers of HBsAg-specific IgG, IgG1, and IgG2a. Conclusions: These findings underscore the advantages of the LNP-PolyI:C adjuvant in enhancing both humoral and cellular immunity, demonstrating its considerable potential as a novel adjuvant. Full article

The moderate pathogenicity coupled with high host susceptibility of Eimeria maxima has precipitated substantial economic losses in the poultry industry. Addressing challenges such as emerging drug resistance underscores the imperative for innovative vaccine strategies. This study developed a novel DNA vaccine to solve this challenge by fusing E. maxima elongation factor-1α (EmEF1α) with chicken chemokine XCL1 (ChXCL1) in the pVAX1 vector. The recombinant plasmid, designated pVAX1-ChXCL1-EmEF1α, was successfully constructed and confirmed to express the ChXCL1-EmEF1α fusion protein in vitro. Immunization of chickens with this DNA vaccine elicited a robust and balanced immune response, characterized by significantly increased proportions of CD4⁺ (11.76%) and CD8⁺ (5.58%) T lymphocytes, elevated levels of Th1-associated cytokines (IFN-γ and IL-12), and strong antigen-specific IgG and IgA antibody responses. Following experimental challenge with E. maxima, vaccinated birds exhibited substantial protection: a 66.4% reduction in oocyst shedding, a 71.7% improvement in relative weight gain, marked attenuation of intestinal lesions, and an anticoccidial index (ACI) of 170. These findings demonstrate that the ChXCL1-EmEF1α DNA vaccine effectively enhances both cellular and humoral immunity. Collectively, this study validates ChXCL1 as a potent molecular adjuvant and establishes the “antigen–adjuvant” fusion DNA platform as a promising strategy for developing next-generation vaccines against avian coccidiosis. Full article

Plaque psoriasis (PP) is a chronic immune-mediated skin disorder characterized by T-cell dysregulation and an imbalance between regulatory T cells (Treg) and T helper 17 (Th17) cells. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), a key inhibitory checkpoint molecule expressed on Treg cells, and its soluble isoform (sCTLA-4) are critical regulators of peripheral immune tolerance and may contribute to PP pathogenesis. This case–control study evaluated the association between the +49 A>G variant of the CTLA4 gene (rs231775) and susceptibility to PP in a mestizo population from western Mexico and assessed serum sCTLA-4 levels. A total of 204 patients with PP and 214 control subjects (CS) were genotyped using PCR-RFLP, and sCTLA-4 concentrations were measured by ELISA. The AG genotype was the most frequent in both groups (49% in PP and 53% in CS), with no significant differences in genotype or allele distributions. Serum sCTLA-4 levels were significantly higher in CS compared to patients (p < 0.05), and no genotype-dependent differences were observed. The rs231775 variant was not associated with PP susceptibility in this population. However, reduced circulating sCTLA-4 levels in patients suggest impaired CTLA-4-mediated immune regulation independent of this variant. Full article

Background/Objectives: Psoriatic disease is a systemic inflammatory condition associated with increased cardiometabolic risk, but the impact of contemporary systemic therapies and narrowband ultraviolet B (NB-UVB) phototherapy on vascular and systemic inflammatory markers remains incompletely characterized. We aimed to systematically synthesize prospective evidence on treatment-associated changes in vascular inflammation and systemic inflammatory biomarkers in adults with moderate-to-severe psoriatic disease. Specifically, we evaluated changes assessed by 18F-FDG PET/CT imaging and circulating biomarkers following biologic therapies or NB-UVB phototherapy. Methods: We systematically searched MEDLINE, Embase, Web of Science, Scopus, and CENTRAL from inception to 31 January 2026 for prospective interventional and observational studies in adults with psoriasis or psoriatic arthritis treated with biologic agents targeting TNF-α, IL-12/23, IL-17, or IL-23, or with NB-UVB phototherapy. Eligible studies were required to report serial assessments of vascular inflammation by 18F-FDG PET/CT (typically aortic target-to-background ratio) and/or systemic inflammatory markers (high-sensitivity C-reactive protein, interleukin-6, TNF-α, GlycA, or hematologic indices such as the neutrophil-to-lymphocyte ratio) over at least 8 weeks of follow-up. We imposed no language restrictions and included only full-text, peer-reviewed prospective studies. Risk of bias was evaluated using RoB 2 for randomized trials and ROBINS-I for nonrandomized studies. Random-effects meta-analyses were prespecified for outcomes reported by at least two clinically comparable studies; however, because of substantial heterogeneity in reporting and methodology, effect estimates were summarized using a structured narrative synthesis. Results: Thirteen prospective studies (n ≈ 900 adults, published 2015–2025) met inclusion criteria, including four studies with serial 18F-FDG PET/CT imaging and one additional PET/CT study providing baseline observational data on vascular inflammation, as well as eight biomarker-focused prospective cohorts. Across randomized mechanistic trials and observational studies, biologic therapies reduced aortic target-to-background ratio by approximately 6–12% over 12–24 weeks (e.g., mean change from 2.42 to 2.18 with TNF-α inhibition and from 2.51 to 2.20 with IL-17 blockade), and no study reported worsening of PET-derived vascular indices under effective systemic treatment. Biologic and other systemic therapies produced concordant reductions in hs-CRP (typically by 30–50%), IL-6, TNF-α, GlycA, and blood-count-derived indices including neutrophil-to-lymphocyte ratio, with biomarker improvements frequently paralleling reductions in cutaneous disease activity and cardiometabolic risk markers. Two NB-UVB cohorts demonstrated significant hs-CRP reductions of roughly 20–30% and modulation of vitamin D-related inflammatory proteins, suggesting systemic anti-inflammatory effects, although these changes appeared less pronounced than with biologic therapy and were not accompanied by vascular imaging. Conclusions: Contemporary systemic psoriasis therapies, particularly biologic agents targeting the IL-23/Th17 axis and TNF-α, are associated with consistent reductions in aortic vascular inflammation and broad improvements in systemic inflammatory biomarkers, whereas NB-UVB phototherapy confers more modest but measurable systemic anti-inflammatory effects, although the current evidence does not allow differentiation between individual biologic classes in terms of magnitude of effect. Although reductions in vascular and systemic inflammatory markers were observed across therapies targeting TNF-α, IL-12/23, IL-17, and IL-23, the small number of mechanistic imaging studies and absence of head-to-head comparisons do not allow robust differentiation between biologic classes or support a uniform class effect. The convergence of imaging and biomarker data reinforces psoriasis as a clinically relevant model of inflammation-driven atherosclerosis and supports the concept that effective control of psoriatic inflammation may contribute to cardiovascular risk modification, highlighting the need for integrated cardiovascular risk assessment in routine care. However, the imaging evidence base remains limited to four small mechanistic PET/CT studies with relatively short follow-up, which constrains the strength and generalizability of conclusions regarding vascular inflammation. Larger, adequately powered, event-driven prospective trials with standardized imaging and biomarker endpoints are needed to determine whether these vascular and systemic anti-inflammatory effects translate into reduced cardiovascular events in psoriatic disease; because of methodological and reporting heterogeneity across the 13 included studies, these conclusions are based on a structured narrative synthesis rather than a formal quantitative meta-analysis. PROSPERO registration number: CRD420261296646. Full article

Static magnetic fields (SMFs) are underexplored as biophysical tools for transplant immunomodulation. This study investigated a 300 mT SMF as a non-pharmacological adjuvant to enhance graft survival in parathyroid xenotransplantation. Human parathyroid tissues were transplanted into Sprague-Dawley rats (n = 20) across four groups: control (G1), SMF-only (G2), transplantation-only (G3), and SMF-assisted transplantation (G4). Following 30-day continuous SMF exposure, functional and immunological assessments were performed. G4 achieved the highest systemic PTH recovery (p = 0.009) without altering intrinsic secretory capacity. Systemic cytokine profiling revealed significant IFN-gamma suppression in G4 (p = 0.0024), suggesting downregulation of Th1-mediated rejection pathways. While G2 showed pro-inflammatory increases (TNF-alpha, GM-CSF), G4 maintained baseline levels, confirming biocompatibility. IHC confirmed that SMF exposure sequestered lymphocytes to the graft periphery, preventing the diffuse infiltration observed in G3. In conclusion, continuous SMF exposure modulates the immune microenvironment by altering lymphocyte migration and IFN-gamma signaling. This biophysical strategy provides localized immunoprotection, potentially offering a drug-free alternative to systemic immunosuppression in endocrine tissue transplantation. Full article

Pregnancy loss affects ~15% of couples and often results from embryonic chromosomal abnormalities. Early peripheral biomarkers that signal abnormal development could improve counseling and clinical decision-making. Here, we analyzed early-pregnancy peripheral blood from patients who conceived via assisted reproduction without preimplantation aneuploidy testing. Samples were collected ≤12 weeks’ gestation for complete blood counts with differentials and multiparameter flow cytometry to quantify major lymphocyte subsets (total T, B, cytotoxic T cells, T helpers (Th), Th1, Th2, Th9, Th17, and regulatory T cells (Treg)). Participants were followed until pregnancy resolution (live birth, euploid or aneuploid miscarriage), and immune profiles were compared by outcome using the Kruskal–Wallis test. Exploratory discriminative analyses were performed with significantly different immune cell quantities. Basophils were highest in the aneuploid miscarriage group (n = 26), distinguishing them from both euploid miscarriage (n = 27) and live birth (n = 91). Th9 cells were lower in aneuploid miscarriages compared to euploid miscarriages. Th17 levels were higher in live births compared with both miscarriage groups. Additional aneuploidy-type-specific immune differences were observed. These alterations may reflect maternal immune recognition of a non-viable conceptus and localized immune activation at the fetal–maternal interface. If validated in larger cohorts, these early peripheral markers may help identify pregnancies at risk for miscarriage, particularly those involving chromosomal abnormalities. Full article

Encephalitozoon cuniculi is an atypical, opportunistic, obligate intracellular fungal pathogen that infects vertebrates. It survives within the host by modulating the host immune response. Crotoxin (CTX), a bioactive compound isolated from the venom of Crotalus durissus terrificus, has been reported to modulate immune responses. This study evaluated the effects of CTX on the immune response of mice infected with E. cuniculi. Mice were immunosuppressed with cyclophosphamide (Cy), infected with E. cuniculi spores, and treated with a single dose of CTX on the day of experimental. The animals were euthanized on day 14 post-infection. Levels of T helper (Th1, Th2, and Th17) cytokines were measured in plasma, and macrophage and lymphocyte populations were analyzed in peritoneal lavage fluid and spleen. In addition, histopathological alterations, hepatic fungal burden, and mRNA expression levels of NLRP3 inflammasome–related genes were assessed. CTX upregulated NLRP3 inflammasome expression and increased IL-18 production, while reducing fungal burden in E. cuniculi-infected mice. Moreover, CTX increased the proportions of macrophages and B cells and enhanced IFN-γ expression in CD4⁺ and CD8⁺ T lymphocytes. Collectively, these findings indicate that CTX reduces fungal load in Cy-immunosuppressed mice infected with E. cuniculi by priming the NLRP3 inflammasome complex and upregulating IL-18 production. Full article