Parasite Immunology最新文献

{"title":"Transcriptomic and Proteomic Analyses Show Minimal Role for ST2 on MCPT5-Expressing Mast Cells in Primary Heligmosomoides polygyrus bakeri Infection.","authors":"Nicole W P Ong, Suzanne H Hodge, Christa P Baker, Danielle J Smyth, Tania Frangova, Henry J McSorley","doi":"10.1111/pim.70076","DOIUrl":"10.1111/pim.70076","url":null,"abstract":"<p><p>The IL-33/ST2 pathway is important as part of the type 2 immune response against helminth infections. Mast cells express the highest levels of the IL-33 receptor subunit ST2 of any immune cell, and mast cells can mediate type 2 immune inflammation; however, the role of IL-33-driven mast cell responses in helminth infection is poorly understood. We sought to determine the role of mast cell ST2 expression during Heligmosomoides polygyrus bakeri (Hpb) infection by generating mast cell conditional ST2 knockout (MCPT5^Cre × ST2^f/f, cKO) mice. These mice have normal frequencies of mast cells at steady state but show specific and strong (albeit incomplete) knockdown of ST2 expression on mast cells. On Hpb infection, faecal egg and adult worm burden were similar between cKO and littermate controls, as were mast cell degranulation markers, serum IgE and goblet cell hyperplasia. Therefore, we conclude that mast cell ST2 does not play a dominant role in Hpb infection. To further investigate the immune response to infection in cKO and littermate controls, transcriptomic and proteomic changes were assessed in duodenal tissues in infected versus naïve mice in cKO and control mice. Minimal transcriptomic and proteomic changes were seen between genotypes, whereas substantial changes were seen between naïve and infected mice, regardless of genotype. Hpb infection induced local increases at the transcript and protein level for mast cell proteases (MCPT1 and MCPT2), resistin-like molecules (RELMα and RELMβ) and markers such as the phospholipase PLA2G4C and the pore-forming protein gasdermin C. Bulk proteomic analysis was also searched against the Hpb genome to identify Hpb proteins present in the duodenal tissues. A list of 60 Hpb proteins of interest was identified in infected duodenal samples, of which 18 contain a signal peptide and are present in the excretory/secretory products of Hpb (HES) (likely secretory products including immunomodulatory proteins); 28 proteins are present in HES but do not contain a signal peptide (likely excretory products); and 14 proteins are not present in HES (likely proteins present in the remnants of Hpb within the duodenum). This work thus provides datasets for changes in the mouse intestine due to Hpb infection, at both the transcript and protein level, as well as a dataset of Hpb proteins detectable in the mouse duodenum at day 14 of infection.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"48 4","pages":"e70076"},"PeriodicalIF":2.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13034402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147575139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Regulatory Effect of Histone Deacetylase (HDAC) 1 and 2 on iNOS, IL-6, TNF-α and IL-10 Expression in Canine Macrophages Infected With Leishmania infantum.","authors":"Gabriela Lovizutto Venturin, Lucas Takeshi Siqueira Ito, Gisele Mitsue Umino, Gabriela Torres Rebech, Flávia Lombardi Lopes, Valéria Marçal Felix de Lima","doi":"10.1111/pim.70078","DOIUrl":"10.1111/pim.70078","url":null,"abstract":"<p><p>Zoonotic visceral leishmaniasis is caused by Leishmania (Leishmania) infantum. Dogs are considered the most critical urban reservoirs of L. (L.) infantum due to their high infection rate and direct transmission to humans. The parasite has developed mechanisms to evade the host's defence system by inhibiting macrophage activation, thereby allowing it to replicate and survive. Pathogens such as viruses and bacteria can modify the host's epigenome, thereby facilitating their survival. Cellular reprogramming leads to epigenetic alterations that modulate chromatin, modify histones and DNA methylation, disrupt normal progression and compromise the continuity of cell differentiation. Histone deacetylases (HDACs) remove lysine acetyl groups from histones, resulting in chromatin alteration and gene silencing. Histone acetyltransferases regulate their function. In this study, we analysed the involvement of HDAC-1 in the defen mechanisms of DH82 macrophages infected with L. infantum. We observed that L. infantum infection increases HDAC1 levels and expression. Silencing HDAC1 with siRNA and the pharmacological inhibitor NaB decreased parasite load and increased iNOS expression, associated with increased histone acetylation at the iNOS promoter. The pharmacological inhibitor NaB also decreased IL-6, IL-10 and TNF-α levels in the culture supernatant of DH82 macrophages infected with L. infantum. Together, these findings indicate that L. infantum-induced HDAC1 upregulation modulates the expression of key innate immune response genes, contributing to the establishment of infection in canine macrophages.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"48 4","pages":"e70078"},"PeriodicalIF":2.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13051526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147623521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered Chemokine Receptor Expression in CD4⁺ T Cells: A Signature of Visceral Leishmaniasis.","authors":"Shreya Upadhyay, Shashi Kumar, Shashi Bhushan Chauhan, Ritirupa Roy, Aziza Neyaz, Siddharth Sankar Singh, Rahul Tiwari, Susanne Nylen, Christian Engwerda, Shyam Sundar, Rajiv Kumar","doi":"10.1111/pim.70077","DOIUrl":"https://doi.org/10.1111/pim.70077","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Robust T helper 1 (Th1) cell responses, which activate macrophages to kill intracellular parasites, are required to control Leishmania infection. Yet, visceral leishmaniasis (VL) patients do not control the infection despite the expansion of CD4&lt;sup&gt;+&lt;/sup&gt; T cells and increased IFN-γ expression in the spleen. Chemokines and/or chemokine receptors are involved in cellular migration and are critical in the inflammatory response. In a recent study that defined a transcriptional signature for CD4&lt;sup&gt;+&lt;/sup&gt; T cells from active VL patients, we found several differentially expressed chemokine receptor genes in CD4&lt;sup&gt;+&lt;/sup&gt; T cells compared to healthy endemic controls (EC). Since CD4&lt;sup&gt;+&lt;/sup&gt; T cells play crucial roles in parasite clearance, a better understanding of the role of altered chemokine receptor expression on CD4&lt;sup&gt;+&lt;/sup&gt; T cells and their different subsets during VL could inform future treatment strategies. In this study, we examined the gene expression and surface protein expression of differentially expressed chemokine receptors found in human VL subjects, relative to endemic controls (EC) by real-time qPCR and multicolor flow cytometry, respectively. We measured chemokine levels in plasma by enzyme-linked immunosorbent assay (ELISA) and performed transwell migration assays and flow cytometry to measure the migratory potential of CD4&lt;sup&gt;+&lt;/sup&gt; T cell subsets. We found elevated mRNA and surface protein expression of CCR5, while reduced CCR4 and CCR6 expression in CD4&lt;sup&gt;+&lt;/sup&gt; T cells from VL patients compared to EC. The frequency of CCR5 expressing Th1 cells was increased in peripheral blood, indicating the expansion of CCR5&lt;sup&gt;+&lt;/sup&gt; Th1 cells that may be responsible for Th1 cells trafficking towards infected tissues. Lower CCR4 expression was found on regulatory T (Treg) cells and central memory T (Tcm) cells, possibly explaining the reduced frequencies of these cells in peripheral blood during VL. The frequency of CCR6 expressing CD4&lt;sup&gt;+&lt;/sup&gt; T cells was also found to be lower in VL patients. Our results show that VL patients possess unique chemokine receptor expression patterns on the cell surface of CD4&lt;sup&gt;+&lt;/sup&gt; T cells, compared to EC. We also found increased levels of CCL3, CCL5 and CCL20 in VL plasma compared to EC. However, no changes were observed for CCL17 levels in VL plasma compared to EC, but their levels increased following treatment. We also observed reduced migration of VL CD4&lt;sup&gt;+&lt;/sup&gt; T cells, relative to other lymphocytes and mononuclear cells, irrespective of exogenous CCL5 presence. However, the frequency of CD4&lt;sup&gt;+&lt;/sup&gt; T cells migrating in response to CCL5 in EC individuals was similar. Additionally, we noted the frequency of CCR5&lt;sup&gt;+&lt;/sup&gt; Th1 cells was increased in VL patients compared to EC. However, no enhancement was seen in the migratory capacity of CCR5&lt;sup&gt;+&lt;/sup&gt; CD4&lt;sup&gt;+&lt;/sup&gt; T cells in the presence of recombinant CCL5. This suggests that the CCR5 receptor signalling pa","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"48 4","pages":"e70077"},"PeriodicalIF":2.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147628325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serological Detection of Canine Toxocarosis Using Recombinant and Native Toxocara canis Excretory-Secretory Antigens: A Comparative ELISA Study.","authors":"Kaveri Theerthagiri Kavitha, Chirukandoth Sreekumar, Manickam Asokkumar, Manivasagam Aravind, Angappan Mangala Gowri","doi":"10.1111/pim.70079","DOIUrl":"https://doi.org/10.1111/pim.70079","url":null,"abstract":"<p><p>Toxocara canis is the most prevalent intestinal roundworm of dogs and other canids, with significant zoonotic potential for humans. In the present study, two recombinant antigens, rTc-CTL-1 and rTES-120, were developed from the larvae of T. canis excretory-secretory (TES) antigens by amplifying, cloning and expressing the respective genes in Escherichia coli. The native TES antigen was prepared from in vitro cultivation of larvae. A total of 170 serum samples were collected from dogs above 6 months of age (n = 90) and below 6 months of age (n = 80) in the Chennai region, Tamil Nadu. The serodiagnostic potential of the recombinant rTc-CTL-1 and rTES-120 antigens was compared with that of the native TES antigen using ELISA for the detection of anti-Toxocara IgG antibodies. The rTc-CTL-1 antigen-based ELISA showed that 40% of dogs above 6 months and 28.8% of dogs below 6 months were positive, whereas the rTES-120 antigen detected 35.6% and 22.5% positivity in the respective age groups. In comparison, the native TES antigen-based ELISA detected 58.9% positivity in dogs above 6 months and 38.8% in dogs below 6 months of age. Among the three antigens, the highest percentage of seropositivity as well as the highest antibody titre was detected with the native TES antigen, followed by the recombinant rTc-CTL-1 antigen and the lowest with the TES-120 antigen. Statistical analysis showed a highly significant difference in seropositivity between the recombinant and native TES antigens (χ² = 15.52, p < 0.01), while no significant difference was observed between the recombinant antigens (χ² = 1.09, p > 0.05). However, a highly significant difference was observed between the age groups of dogs when using the native TES antigen (χ² = 6.87, p < 0.01). Detection of T. canis eggs in faecal samples revealed that only 12.2% of adult dogs were positive, whereas 60% of pups were positive. In contrast, the IgG ELISA test detected more positive cases in adult dogs compared to faecal examination. It was concluded that the IgG-based ELISA using either recombinant or native TES antigens is a reliable tool for detecting migratory larval infection in adult dogs, with a fairly high degree of sensitivity.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"48 4","pages":"e70079"},"PeriodicalIF":2.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147628331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison Between Phenotypic Profile and Functional Aspects of IL-9-Producing Lymphocytes, Th17 and Tfh of Individuals From Endemic and Non-Endemic Areas for Hookworm Infection.","authors":"Yvanna Louise Di Christine Oliveira, Marcelo Eduardo Cardozo, Luisa Mourão Dias Magalhães, Carlos Thailan de Jesus Santos, Ramayana Morais de Medeiros Brito, Luciana Maria de Oliveira, Ana Carolina Amado Gomes, Vinícius Torres Castro Campos, Ricardo Toshio Fujiwara, Silvio Santana Dolabella, Lilian Lacerda Bueno","doi":"10.1111/pim.70070","DOIUrl":"10.1111/pim.70070","url":null,"abstract":"<p><p>Hookworm infections remain a major public health concern in endemic areas, modulating both the adaptive and innate immune systems. While the type 2 response is well-characterised, the roles of T follicular helper (Tfh), Th17, and IL-9-producing lymphocytes remain poorly defined. Here, we characterised these T cell subsets in individuals naturally infected with hookworms. From 1500 faecal samples screened, 60 were positive for hookworms, and peripheral blood was collected from 10 uninfected controls from endemic (NEG END) and non-endemic (NEG NE) areas, as well as from 7 infected individuals before (HKW BT) and after (HKW PT) treatment. Infected individuals displayed haematological alterations, including anaemia (n = 2), eosinophilia (n = 1), monocytosis (n = 4), and lymphocytosis (n = 3), along with an expansion of PBMCs, particularly Tfh cells, during infection. Expression of IL-9 and IL-10 by Tfh cells was markedly elevated after treatment. In contrast, individuals from non-endemic areas displayed a distinct baseline profile with higher Tfh activation (CD69) expression, suggesting immune adaptation in endemic settings. While IL-10-producing Tfh expanded during infection, IL-9-producing cells and Th17 cells expanded mainly after treatment. These findings suggest that individuals living in endemic areas, regardless of infection status, exhibit signs of persistent antigenic stimulation that promote a more tolerogenic and regulated immune profile. Moreover, hookworm infection and subsequent treatment reshape the immune landscape, highlighting the contribution of Tfh- and Th17-associated pathways, as well as IL-9 and IL-10 production, in modulating host-parasite interactions.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"48 3","pages":"e70070"},"PeriodicalIF":2.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12983440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147444541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring Demodex in Chronic Urticaria: Lack of Association but Evidence for Type-2 Immune Activation in Demodex.","authors":"Burak Celik, Merve Kaya, Selma Emre","doi":"10.1111/pim.70073","DOIUrl":"https://doi.org/10.1111/pim.70073","url":null,"abstract":"<p><p>Chronic spontaneous urticaria (CSU) is a mast cell driven multifactorial disorder with complex pathogenesis. While the association between CSU and internal parasites has been investigated, the association of ectoparasites such as Demodex mites remains elusive. This study aims to compare Demodex prevalence in CSU patients with healthy controls and to evaluate selected immunologic parameters in Demodex patients. A prospective case-control study was conducted including 100 patients with CSU and 50 age- and sex-matched controls. Skin surface biopsy was performed using the cyanoacrylate method, and participants were classified as Demodex-positive if more than five mites were detected within a 1 cm² field. Serum levels of total IgE, eosinophil counts, thyroid-stimulating hormone (TSH), free thyroxine (T4), and anti-thyroid peroxidase (anti-TPO) antibodies were measured. Demodex positivity was observed in 26% of CSU patients and 26% of controls (p = 1.00). Median IgE (208.08 IU/mL, range 4.89-1207.00) and eosinophil counts (0.17 ± 0.07 × 10⁹/L) were significantly higher in Demodex-positive participants than in Demodex-negative ones (65.72 IU/mL, range 2.40-632.11, and 0.14 ± 0.09 × 10⁹/L, respectively; p < 0.05). Thyroid function parameters and antibody levels showed no significant differences between groups. Although Demodex prevalence did not significantly differ between CSU patients and controls, infestation was associated with elevated IgE and eosinophil levels, suggesting a possible association with type 2-skewed immune markers. Further studies with quantitative mite assessment and detailed immunologic profiling are needed to better understand this relationship.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"48 3","pages":"e70073"},"PeriodicalIF":2.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147474981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunopathology of Leishmaniasis: Molecular and Cellular Mechanisms of Tissue Injury Provoked by Chronic Infection.","authors":"Claudio M Lezama-Dávila, Angélica P Isaac-Márquez","doi":"10.1111/pim.70066","DOIUrl":"https://doi.org/10.1111/pim.70066","url":null,"abstract":"<p><p>Human infections caused by parasites represent a serious worldwide health issue, especially in underdeveloped countries. According to the World Health Organization, Leishmania ssp. is responsible for more than 70,000 deaths worldwide, mostly due to untreated visceral leishmaniasis (VL). Other species that cause non-deadly cutaneous infections are also relevant; they frequently leave disfiguring scars in infected patients, as seen in those with mucocutaneous leishmaniasis (MCL) or localised cutaneous leishmaniasis (LCL). Mechanisms of tissue injury provoked by chronic infections with different Leishmania ssp. correlate with immunological imbalances in the cellular and humoral immunological milieu. This parasite triggers host responses, including the activation of antibodies and complement, programmed cell death, uncontrolled cytokine synthesis, the production of reactive oxygen species and inflammation. If these responses are correctly balanced, they protect the infected host against chronic infection and relapse. However, when the right balance between these biological responses is disrupted, tissue damage occurs and frequently results in the death of those suffering from untreated VL or leaving disfiguring scars in MCL and LCL patients. Here, we review important mechanisms of tissue damage triggered by Leishmania species of human interest.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"48 3","pages":"e70066"},"PeriodicalIF":2.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147309020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thymic Atrophy Development in a Non-Lethal Plasmodium Infection.","authors":"G M Corral-Ruiz, M J Pérez-Vega, I Mancilla-Herrera, J Barrios-Payán, L Fabila-Castillo, R Hernández-Pando, L E Sánchez-Torres","doi":"10.1111/pim.70071","DOIUrl":"https://doi.org/10.1111/pim.70071","url":null,"abstract":"<p><p>The thymus is a vital organ for T-cell development that undergoes significant changes during malaria infection, including atrophy and disrupted structure, which weaken immune responses. This study examines the mechanisms behind thymic atrophy during Plasmodium chabaudi AS infection, focusing on cellular and molecular changes across different parasitemia stages. Our results show that thymic atrophy is marked by a substantial decrease in thymus weight and cellularity, especially at 20%-30% parasitemia levels. A significant loss of DP and SP thymocytes mainly causes this atrophy. Histological analysis revealed notable cortical shrinkage and DNA fragmentation in thymic cells, indicating increased apoptosis. Elevated serum cytokines and chemokines, including IFN-γ, TNF-α, IL-6 and CXCL9, were observed throughout the infection, with higher levels correlating with the degree of thymic atrophy. Also, early release of thymocytes into peripheral tissues, especially the spleen, worsened the decrease in thymic cellularity. However, after parasitemia resolved, the thymus recovered, restoring its structure and thymocyte populations. These results highlight the complex interaction between parasite-induced inflammation and immune cell behaviour, suggesting that even though P. c. chabaudi AS infection is not lethal, a prolonged parasitic burden can cause severe thymic dysfunction, possibly impairing immune system function.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"48 3","pages":"e70071"},"PeriodicalIF":2.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147513922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioenergetic Profiling of Lymphocytes in Patients With Visceral Leishmaniasis (VL) and Post Kala-Azar Dermal Leishmaniasis (PKDL).","authors":"Shilpa Sengupta, Mitali Chatterjee","doi":"10.1111/pim.70069","DOIUrl":"https://doi.org/10.1111/pim.70069","url":null,"abstract":"<p><p>Studies pertaining to Visceral leishmaniasis (VL) and its dermal sequel, Post Kala-azar Dermal Leishmaniasis (PKDL) are usually restricted to their immunopathogenesis, but the role, if any, regarding metabolic dysfunction of lymphocytes remains unanswered, and was the focus of this study. To delineate and correlate the functional and bioenergetic status of lymphocytes in patients with VL and PKDL. In Peripheral blood of patients with VL (n = 11) or PKDL (n = 18), along with healthy controls (n = 10), the T lymphocyte subsets (CD4⁺ and CD8⁺), their activation (CD69) and exhaustion (CD279) status were determined by flow cytometry. Oxidative phosphorylation (OXPHOS) and glycolysis were measured concomitantly in an extracellular flux analyser, whilst the status of mitochondrial respiration and glycolysis related genes was measured by qPCR. In comparison to healthy controls, the activation status remained unchanged in VL and PKDL cases but the frequency of exhausted T cells was significantly raised. These exhausted T cells showed an increased expression of OXPHOS in terms of signalling markers (SMAD3 and CPT1A) and oxygen consumption rate (OCR), along with an increased expression of mitochondrial respiration genes, which correlated positively with CD279⁺ T cells, whereas glycolysis remained unchanged. Patients with VL and PKDL demonstrated increased expression of CD279/Programmed cell death protein 1 (PD-1). This PD-1 signalling possibly activated SMAD3 and mitochondrial CPT1A, which led to increased mitochondrial respiration. This metabolic adaptation possibly facilitated sustenance of the exhausted T cell phenotype and contributed to disease progression. Targeting immunometabolism could well be a therapeutic approach worthy of future pharmacological consideration.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"48 3","pages":"e70069"},"PeriodicalIF":2.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147434704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amblyomma cajennense Sensu Stricto (Fabricius, 1787) and Amblyomma sculptum (Berlese, 1888) Tick Saliva Elicit Immune-Modulatory Activity in Isolated Murine Macrophages With an Insight Into Proteomic Analysis.","authors":"André de Abreu Rangel Aguirre, Valdison Pereira Dos Reis, Sulamita da Silva Setúbal, Angélica Lorena Pereira Mendes Carioca, Ketlei Monteiro Tavares, Geisa Paulino Caprini Evaristo, Joseph Albert Medeiros Evaristo, Fábio César Sousa Nogueira, Jansen Fernandes Medeiros, Juliana Pavan Zuliani","doi":"10.1111/pim.70072","DOIUrl":"10.1111/pim.70072","url":null,"abstract":"<p><p>Tick saliva is known to cause immunosuppression and help pathogen transmission. Amblyomma sculptum is a public health concern as a vector of Rickettsia rickettsii. Another close-related species is Amblyomma cajennense sensu stricto (s.s.). The impact of saliva from these species on murine macrophages remains unclear. This study evaluated saliva from A. cajennense s.s. and A. sculptum in murine peritoneal macrophages, assessing cell viability, adhesion, morphology, reactive oxygen species (ROS) production, phagocytosis and cytokine secretion. Additionally, a proteomic analysis was conducted and the proteins that were secreted in salivas were estimated. Neither A. sculptum nor A. cajennense s.s. saliva did it affect viability, adhesion or morphology, but increased ROS production and phagocytic activity. A. sculptum saliva decreased IL-1β and increased TNF-α, whereas A. cajennense s.s. saliva increased IL-6 and IL-10. Proteomic analysis revealed 221 and 303 secreted proteins in A. cajennense s.s. and A. sculptum, respectively and the more abundant were vitellogenins, microplusins, serpins, cystatins, actin, beta actin and calponins. These findings suggest that saliva from each species modulates macrophage activity in distinct ways, eliciting pro- and anti-inflammatory responses. This is the first comparative evaluation of salivas from two species of the A. cajennense sensu lato complex, providing new insights into their interaction with innate immune cells.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"48 3","pages":"e70072"},"PeriodicalIF":2.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13016862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147513919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}