Cellular immunology最新文献

{"title":"Nebulized mesenchymal stem cell-derived exosomes attenuate airway inflammation in a rat model of chronic obstructive pulmonary disease","authors":"Min Wang ,&nbsp;Yuxin Hao ,&nbsp;Wei He ,&nbsp;Hui Jia ,&nbsp;Zhaoshuang Zhong ,&nbsp;Shuyue Xia","doi":"10.1016/j.cellimm.2025.104933","DOIUrl":"10.1016/j.cellimm.2025.104933","url":null,"abstract":"<div><div>Chronic Obstructive Pulmonary Disease (COPD) is one of the leading causes of death worldwide, and current treatments fail to significantly halt its progression. Exosomes derived from mesenchymal stem cells (MSCs-Exos) have demonstrated promising potential in treating COPD due to their anti-inflammatory and regenerative biological properties. In this study, we investigated the potential anti-inflammatory effects of bone marrow mesenchymal stem cell-derived exosomes (BMSCs-Exos) in a COPD rat model and the possible mechanisms by which they inhibit airway remodeling, as well as identifying the optimal dosage and administration route. Our results show that nebulized BMSC-Exos significantly improve lung function in COPD rats while reducing pulmonary inflammatory infiltration, bronchial mucus secretion, and collagen deposition. Moreover, BMSC-Exos treatment notably decreased the expression of pro-inflammatory cytokines such as TNF-α, IL-6 and IL-1β, and the pro-fibrotic factor TGF-β1 in serum, bronchoalveolar lavage fluid (BALF), and lung tissue. The most pronounced therapeutic effect was observed at a low dose of exosomes. Furthermore, quantitative real-time PCR and immunohistochemical analyses revealed that nebulized BMSC-Exos significantly inhibited airway remodeling and epithelial–mesenchymal transition (EMT) by suppressing the Wnt/β-catenin signaling pathway. In conclusion, these findings indicate that nebulized BMSC-Exos offer a noninvasive therapeutic strategy for COPD by mitigating lung inflammation and airway remodeling through the suppression of abnormal Wnt/β-catenin pathway activation induced by cigarette smoke (CS) and lipopolysaccharide (LPS) in rats.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"409 ","pages":"Article 104933"},"PeriodicalIF":3.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509101","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":"Breast cancer stem cells convert anti-tumor CD4+ T cells to pro-tumor T regulatory cells: Potential role of exosomal FOXP3","authors":"Udit Basak ,&nbsp;Sourio Chakraborty ,&nbsp;Sumon Mukherjee ,&nbsp;Subhadip Pati ,&nbsp;Poulami Khan ,&nbsp;Subhajit Ghosh ,&nbsp;Arghya Adhikary ,&nbsp;Kuladip Jana ,&nbsp;Gaurisankar Sa ,&nbsp;Tanya Das","doi":"10.1016/j.cellimm.2025.104931","DOIUrl":"10.1016/j.cellimm.2025.104931","url":null,"abstract":"<div><div>Cancer progression and its treatment-response are regulated by the tumor microenvironment (TME). Tumor-initiating cancer stem cells (CSCs) remain in constant communication with the TME, and modulate it through several mechanisms. Here, from <em>in-silico</em> findings and analyzing breast cancer patient tissue-derived data, CSCs and Tregs were found to be positively correlated. Furthermore, our <em>in-silico</em> analyses highlighted a positive relationship between CSC genes and Treg signature marker, FOXP3, even in cancer cell lines that do not contain any T cell or Treg cells, thus raising the possibility of CSCs expressing FOXP3. Validating our hypothesis, higher expression of FOXP3, both at mRNA and protein levels, was observed in breast CSCs than non-stem cancer cells. Since a small population of CSCs initiate tumor in immune cell-dominated TME, we aimed at exploring whether breast CSCs directly transfer FOXP3 to CD4⁺T cells to generate immunosuppressive Treg cells. First, our search revealed CSC-derived exosomes (CDEs) generated CD4⁺CD25⁺FOXP3⁺ Tregs at an early time-point of 24 h, which were immunosuppressive in nature. Next, detecting presence of FOXP3 protein in CDEs showed a strong possibility of FOXP3 transfer through CDEs. This was supported by detecting elevated FOXP3 levels from 12 h in translation inhibitor-treated T cells upon CDE-exposure. Finally, exosomes derived from FOXP3 attenuated-CSCs furnished lower FOXP3 in T cells than control CDEs. This mechanism was validated in <em>in-vivo</em> murine model. Together these results indicate a hitherto unexplored role of CSC-derived FOXP3 in reprogramming T cells into immunosuppressive Treg cells.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"409 ","pages":"Article 104931"},"PeriodicalIF":3.7,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143453338","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":"In vitro ovarian tumor-conditioned CD163+ human macrophages retain phagocytic response to CD47 blockade","authors":"Kristian W. Antonsen ,&nbsp;Anne G. Jensen ,&nbsp;Boe S. Sorensen ,&nbsp;Anders Etzerodt ,&nbsp;Søren K. Moestrup ,&nbsp;Holger J. Møller","doi":"10.1016/j.cellimm.2025.104932","DOIUrl":"10.1016/j.cellimm.2025.104932","url":null,"abstract":"<div><h3>Introduction</h3><div>CD163-expressing macrophages are abundant in ovarian cancer where they accelerate tumor growth and metastasis. CD47 blockade is a novel immunotherapy aiming to activate macrophage phagocytosis of tumor cells, but it is currently unknown if the tumor-associated macrophages expressing CD163 respond poorly to CD47 blockade.</div></div><div><h3>Methods</h3><div>Human monocyte-derived macrophages were exposed to tumor-conditioned medium from A2780 ovarian cancer cells during differentiation. Effects on gene expression, membrane protein levels, release of soluble proteins and macrophage phagocytosis of A2780 cells in response to CD47 blockade were measured and compared to control macrophages.</div></div><div><h3>Results</h3><div>Tumor cell conditioning induced macrophage expression of CD163 on both the mRNA and protein level. Furthermore, tumor conditioning simultaneously increased protein expression of the phenotype markers CD206 and CD80, and the phagocytosis checkpoint LILRB1. However, tumor conditioning did not reduce phagocytic capacity, as CD47 blockade induced macrophage phagocytosis of A2780 cells to similar degrees in both control and tumor cell-conditioned macrophages.</div></div><div><h3>Discussion</h3><div>In vitro tumor conditioning did not reduce the phagocytic response to CD47 blockade, suggesting that induction of a macrophage phenotype with increased expression of CD163 does not directly limit the capacity for phagocytosis of tumor cells. In conclusion, these findings suggest that CD163+ macrophages remain responsive to CD47 blockade, highlighting their potential as targets for immunotherapy in ovarian cancer.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"409 ","pages":"Article 104932"},"PeriodicalIF":3.7,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143464189","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 polarization of macrophages participates in the repair after folic acid-induced acute kidney injury","authors":"Shujie Yang ,&nbsp;Yan Shen","doi":"10.1016/j.cellimm.2025.104929","DOIUrl":"10.1016/j.cellimm.2025.104929","url":null,"abstract":"<div><div>Acute kidney injury (AKI) remains a major public health challenge, posing serious threats to human health. Increasing evidence indicates that renal cells undergo significant metabolic alterations following AKI, with inflammatory responses persisting throughout both injury and repair phases. Our previous research has demonstrated that heightened aerobic glycolysis after AKI leads to increased secretion of metabolic byproducts such as lactate, which plays a critical role in tissue repair. However, the relationship between metabolic reprogramming and inflammatory responses, as well as the underlying mechanisms, remain poorly understood. This study aims to clarify the regulatory effects of the glycolytic byproduct lactate on macrophage activation and phenotypic differentiation following AKI. We observed increased expression of M1/M2 macrophages and elevated secretion of inflammatory cytokines after folic acid-induced AKI. Immunofluorescence staining showed co-localization of macrophages with α-SMA. Manipulating lactate levels post-injury led to a decrease in macrophage expression and a reduction in fibroblast activation and proliferation, ultimately impairing renal tissue repair. These findings suggest that targeting lactate as a key regulator of macrophage phenotype differentiation may provide a theoretical and clinical foundation for therapeutic strategies in AKI repair.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"409 ","pages":"Article 104929"},"PeriodicalIF":3.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143376788","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":"Tim-3 promotes viral infection by suppressing the USP25-TRAF3-IRF7 signaling pathway","authors":"Lin Du ,&nbsp;Jinjie Chen ,&nbsp;Chunxiao Du ,&nbsp;Junrui Chen ,&nbsp;Zhaoxiang Wang ,&nbsp;Bing Bao ,&nbsp;L.V. Zhonglin ,&nbsp;Chen Xing ,&nbsp;Meng Liang ,&nbsp;Lanying Wang ,&nbsp;Shun Xie ,&nbsp;Yuxiang Li ,&nbsp;Zhiding Wang ,&nbsp;Ge Li ,&nbsp;Jun Zhang ,&nbsp;Gencheng Han","doi":"10.1016/j.cellimm.2025.104930","DOIUrl":"10.1016/j.cellimm.2025.104930","url":null,"abstract":"<div><div>Tim-3, an immune checkpoint inhibitor, plays key roles in maintaining immune homeostasis and is involved in viral evasion. However, the precise role of Tim-3 in viral infection remains to be determined. USP25 is a deubiquitinating enzyme that initiates antiviral immunity by deubiquitinating TRAF3 and triggering the antiviral signaling pathway. Here we found that Tim-3-specific knockout in myeloid cells leads to enhanced antiviral immunity in mice with vesicular stomatitis virus (VSV) encephalitis by increasing the type I interferon response. Mechanistically, Tim-3 inhibits the expression of USP25 via STAT1 and interacts with USP25 but does not regulate its posttranslational modification; as a result, Tim-3 inhibits USP25-mediated deubiquitination of TRAF3, promotes K48-linked ubiquitination and degradation of TRAF3, inhibits the phosphorylation of IRF7, and ultimately downregulates the interferon response. These findings provide new insights into the function of Tim-3 in antiviral immunity and its related clinical significance.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"409 ","pages":"Article 104930"},"PeriodicalIF":3.7,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143395544","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":"Sodium butyrate prevents lipopolysaccharide induced inflammation and restores the expression of tight junction protein in human epithelial Caco-2 cells","authors":"Jyotsana Bakshi,&nbsp;K.P. Mishra","doi":"10.1016/j.cellimm.2024.104912","DOIUrl":"10.1016/j.cellimm.2024.104912","url":null,"abstract":"<div><div>The gastrointestinal (GI) tract is susceptible to damage under high altitude hypoxic conditions, leading to gastrointestinal discomfort and intestinal barrier injury. Sodium butyrate, a short-chain fatty acid present as a metabolite in the gut, has emerged as a promising therapeutic agent due to its ability to act as an immunomodulatory agent and restore intestinal barrier integrity. This study aimed to explore the mechanism by which sodium butyrate exhibits anti inflammatory effect on intestinal epithelial cells. <em>In vitro,</em> Caco-2 epithelial cells and RAW 264.7 macrophages were used to investigate the protective role of sodium butyrate on Lipopolysaccharide (LPS) induced inflammation. Cell viability assays demonstrated that 1 mM (110.86 μg/mL) of sodium butyrate did not exhibit cytotoxicity on cells <em>in vitro</em>. Treatment with sodium butyrate suppressed reactive oxygen species levels and TNF-α production in LPS-stimulated macrophages, indicating its efficacy in mitigating inflammatory responses. Western blot analysis revealed that sodium butyrate attenuated the expression of iNOS in RAW 264.7 macrophage cells. Moreover, sodium butyrate also reversed the LPS induced over expression of HIF-1α, NLRP3, IL-1β as well as NF-kB in Caco-2 epithelial cells and also had a suppressive effect on IL-8 secretion after LPS stimulation. Immunocytochemistry demonstrated that sodium butyrate enhanced tight junction protein occludin expression in Caco-2 cells while also restoring the decreased permeability of the Caco-2 monolayer due to LPS. These results indicate that sodium butyrate may influence immune responses by suppressing inflammatory mediators and improving the integrity of the epithelial barrier. Understanding the intricate interactions between gut metabolites and host immune responses may help in the development of innovative therapeutic strategies to alleviate intestinal inflammation in high altitude environments.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"408 ","pages":"Article 104912"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892464","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":"Berberine shaping the tumor immune landscape via pyroptosis","authors":"Jinjin Xie ,&nbsp;Xin Du ,&nbsp;Yuke Li ,&nbsp;Chengyu Wu ,&nbsp;Rui Li ,&nbsp;Mengnan Zhao ,&nbsp;Sanjun Shi","doi":"10.1016/j.cellimm.2024.104908","DOIUrl":"10.1016/j.cellimm.2024.104908","url":null,"abstract":"<div><div>Pyroptosis is a programmed cell death (PCD) mainly mediated by the Gasdermin family of proteins, among which Gasdermin E (GSDME) is considered a tumor suppressor gene. GSDME can recruit immune cells to the tumor microenvironment (TME) and promote their effects. Activating and enhancing adaptive immunity through GSDME is a potential solution for anti-tumor therapy. Here we reported that berberine (BBR), a small molecule from traditional Chinese medicine, as a GSDME activator, induced caspase-3 (C-3)/GSDME pathway-mediated pyroptosis through the mitochondrial pathway, improved the immunosuppressive state of the tumor microenvironment, and thus promoted anti-tumor immunity. We determined the induction of pyroptosis of 4 T1 cells by BBR through various experiments, and investigated the immune activation effect of BBR by co-culture <em>in vitro</em>, which induced DCs maturation and macrophage polarization. Zebrafish embryo toxicity experiments were used to evaluate the <em>in vivo</em> safety of berberine. Furthermore, the <em>in vivo</em> antitumor and immune activation effects of BBR were investigated using 4 T1 orthotopic model mice, and the results showed that BBR could eliminate orthotopic tumor cells by activating local and systemic immunity. Moreover, we observed that BBR significantly inhibited breast cancer lung metastasis. In summary, our results showd the role of BBR as a GSDME activator stimulated both local and systemic antitumor immune responses by inducing pyroptosis, effectively preventing tumor development and metastasis.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"408 ","pages":"Article 104908"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863322","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":"Bacteriophage derived dsRNA induces polarized activation of alveolar macrophages from Balb/c and C57Bl/6 mice in vitro in sex- and age-dependent manner","authors":"R. Dovhyi ,&nbsp;A. Dvukhriadkina ,&nbsp;K. Ostrovska ,&nbsp;M. Rudyk ,&nbsp;Irina Verhovcova ,&nbsp;Kristine Vaivode ,&nbsp;D. Pjanova ,&nbsp;L. Ostapchenko ,&nbsp;L. Skivka","doi":"10.1016/j.cellimm.2025.104916","DOIUrl":"10.1016/j.cellimm.2025.104916","url":null,"abstract":"<div><div>Bacteriophage-derived dsRNA (bp-dsRNA), also known as Larifan, is a poly-functional and wide-spectrum antiviral medication with potent interferonogenic activity. In the lungs of golden Syrian hamsters infected with SARS-CoV-2, Larifan substantially reduces viral load and decreases infection-induced pathological lesion severity. Alveolar macrophages (AM) are key sentinel cells in the lung, which play an important role in antiviral innate immune responses and, at the same time, can trigger infection-associated hyper-inflammatory response. This study revealed that treatment with bp-dsRNA (Larifan) <em>in vitro</em> modulates the functional profile of AM from intact Balb/c and C57Bl/6 mice. The pattern of the drug response depends on the animal strain, age and sex. AM from Balb/c mice generated a weaker response to the preparation as compared to cells from C57Bl/6 mice. Most emphatic responses to the treatment with bf-dsRNA (Larifan) were registered in AM from old males of both BALB/c and C57BL/6 strains with the strongest in the latter. AM from old C57BL/6 females were less likely to be influenced by the preparation. In most cases, exposure to bf-dsRNA (Larifan) increased AM phagocytic activity and was more often accompanied by the stimulation of intracellular reactive oxygen species generation, than by its decrease. In most animal groups, treatment with bf-dsRNA (Larifan) did not affect significantly CD206 expression and down-regulated CD80 expression in AM. Taken together, our findings suggest that bf-dsRNA (Larifan) not so much stimulates the bivalent phenotype of AM, as restrains their hyper-inflammatory responses through the control of antigen-presentation while preserving functional signatures typical of patrolling tissue-resident macrophages.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"408 ","pages":"Article 104916"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142945543","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":"P2RX1-blocked neutrophils induce CD8+ T cell dysfunction and affect the immune escape of gastric cancer cells","authors":"Yan Zhang ,&nbsp;Fenglin Zhang ,&nbsp;Zhi Liu ,&nbsp;Min Li ,&nbsp;Ge Wu ,&nbsp;Hui Li","doi":"10.1016/j.cellimm.2024.104901","DOIUrl":"10.1016/j.cellimm.2024.104901","url":null,"abstract":"<div><h3>Background</h3><div>Gastric cancer (GC) is one of the deadly malignancies of the gastrointestinal tract. Research has confirmed the linkage of P2RX1 with immune cell activation and tumor progression. This project focused on the impact of P2RX1 level in neutrophils on the efficacy of immune checkpoint inhibitor (ICI) treatment in GC.</div></div><div><h3>Methods</h3><div>Blood samples from 23 GC patients eligible for camrelizumab treatment were collected. Flow cytometry was carried out to analyze the proportion of P2RX1 in neutrophils. IHC was utilized to detect the expression level of PD-L1. We also evaluated the chemotaxis ability of neutrophils using a Transwell system, assessed the viability and apoptosis rate of GC cells using CCK-8 and flow cytometry, measured the proportions of CD8⁺PD-1⁺ and CD8⁺GZMB⁺ cells, determined the expression levels of IL-6, TNFα, IFN-γ, IL-8, IL-12, IL-1β, and GZMB by utilizing enzyme-linked immunosorbent assay (ELISA), and examined the expression levels of P2RX1 and PD-L1 using western blot (WB). By establishing a xenograft mouse model, we studied the impact of P2RX1-blocked neutrophils on the efficacy of ICI treatment in the GC microenvironment.</div></div><div><h3>Results</h3><div>In GC, clinical analysis revealed increased infiltration of P2RX1-lowly expressed neutrophil subsets and increased expression of PD-L1. <em>In vitro</em> experiments demonstrated that abnormal expression of P2RX1 affected neutrophil function. Furthermore, the blockage or knockdown of P2RX1 in neutrophils modulated CD8⁺ T cell function, promoting GC progression. In <em>in vivo</em> experiments, the blockage of P2RX1 in neutrophils inhibited the effectiveness of ICI treatment in the GC microenvironment.</div></div><div><h3>Conclusion</h3><div>This project validated that the loss of P2RX1 in neutrophils induces CD8⁺ T cell dysfunction and affects the GC development, indicating that P2RX1 may be an accurate biomarker for predicting ICI response, thus providing a theoretical basis for the clinical application of ICI.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"408 ","pages":"Article 104901"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827181","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":"Enhanced apoptosis and inflammation allied with autophagic and apoptotic Leishmania amastigotes in the seemingly undamaged ear skin of clinically affected dogs with canine visceral Leishmaniasis","authors":"Barbara Laurice Araújo Verçosa ,&nbsp;Maria Imaculada Muniz-Junqueira ,&nbsp;Ana Lys Bezerra Barradas Mineiro ,&nbsp;Maria Norma Melo ,&nbsp;Anilton Cesar Vasconcelos","doi":"10.1016/j.cellimm.2024.104909","DOIUrl":"10.1016/j.cellimm.2024.104909","url":null,"abstract":"<div><div>Programmed cell death plays a relevant role in the pathogenesis of visceral Leishmaniasis. Apoptosis selects suitable parasites, regulating parasite density, whereas autophagy eliminates pathogens. This study aimed to assess the inflammation and apoptosis in inflammatory cells and presents a unique description of the presence of autophagic and apoptotic <em>Leishmania</em> amastigotes in naturally <em>Leishmania-</em>infected dogs. Fragments from seemingly undamaged ear skin of sixteen <em>Leishmania</em>-infected dogs and seven uninfected dogs were evaluated through histomorphometry, ultrastructural, immunohistochemical and transmission electron microscopy (TEM) analyses. <em>Leishmania</em> amastigotes were present on seemingly undamaged ear skin only in clinically affected dogs. Parasite load, morphometrical parameters of inflammation and apoptotic index of inflammatory cells were higher in clinically affected animals and were related to clinical manifestations. Apoptotic index and morphometric parameters of the inflammatory infiltrate in undamaged ear skin were positively correlated with parasite load. Apoptotic and non-apoptotic <em>Leishmania</em> amastigotes were observed within neutrophils and macrophages. <em>Leishmania</em> amastigotes were positive for Bax, a marker for apoptosis, by immunohistochemistry. Morphological characteristics of apoptosis and autophagy in <em>Leishmania</em> amastigotes were observed only in phagocytes of clinically affected dogs. Positive correlations were found between histomorphometry and clinical manifestations. Our results showed that apoptosis and autophagy in <em>Leishmania</em> amastigotes may be related to both the increase in parasite load and apoptotic index in inflammatory cells, and with the intensity of the inflammatory response in clinically affected dogs. Thus, our study suggests that apoptotic and autophagy <em>Leishmania</em> within phagocytes may have facilitate the survival of the parasite and it appears to play an important role in the process of <em>Leishmania</em> infection.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"408 ","pages":"Article 104909"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863424","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}