Microbes and Infection最新文献

{"title":"FOXP3 gene polymorphisms are associated with indeterminate clinical form of Chagas disease.","authors":"Nayara I Medeiros, Daniela Silva Oliveira, Karine S Ferreira, Tatjana S L Keesen, Luiz Paulo C Rocha, Giovane R Sousa, Marcos P S Damasio, Rafaelle C G Fares-Gusmao, Ana T Chaves, Fernanda F De Araújo, Walderez O Dutra, Rodrigo Correa-Oliveira, Manoel O C Rocha, Juliana A S Gomes","doi":"10.1016/j.micinf.2025.105544","DOIUrl":"10.1016/j.micinf.2025.105544","url":null,"abstract":"<p><p>The forkhead box protein 3 (FOXP3) transcription factor is the main marker of regulatory T-cell (Treg) development and activation, a subpopulation involved in immune system regulation, self-tolerance, and protection against infections. We previously showed that Treg cells control the exacerbated immune response and morbidity in chronic Chagas disease, by modulating the cytokine environment and killing effector cells. Although FOXP3 gene polymorphisms have already been studied in several diseases, their role in Chagas disease is underreported. This study investigated FOXP3 gene polymorphism (rs3761548) in patients with Chronic Chagas disease and the association between FOXP3 polymorphisms (-3279 C/T and -3499 G/T) with clinical forms of the disease. We show that the -3499 G/T polymorphism of the heterozygous genotype (GT) is twice as prevalent in women with indeterminate clinical form (IND). Other analyses showed that the polymorphic allele (T+ -3499 G/T) is high in women with IND, suggesting a protective role for this polymorphism. This pattern is associated with high frequency of FOXP3 in Treg cells in individuals with the IND form. Our results suggest that -3499 G/T polymorphism in the FOXP3 gene may play an important role in T. cruzi infection, contributing to control and the development of the IND clinical form.</p>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":" ","pages":"105544"},"PeriodicalIF":2.6,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340192","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":"Cryptococcus neoformans and the EGFR Puzzle: Uncovering a Novel mechanism for blood-brain barrier crossing.","authors":"Jingyu Zhao, Wei Fang, Yangjie Gao, Zhenzong Fa, Guizhen Wang, Julin Gu","doi":"10.1016/j.micinf.2025.105540","DOIUrl":"10.1016/j.micinf.2025.105540","url":null,"abstract":"<p><p>This study aims to investigate the molecular mechanisms by which Cryptococcus neoformans (C. neoformans) crosses the blood-brain barrier (BBB), focusing specifically on the role of the epidermal growth factor receptor (EGFR) and its ligand, HB-EGF. Cryptococcal meningitis, caused by C. neoformans, has a high mortality rate and poses a significant threat to global public health. Research indicates that C. neoformans employs various strategies to cross the BBB, with transcellular transport being particularly critical. We observed that C. neoformans infection significantly upregulates the expression and phosphorylation of EGFR in brain microvascular endothelial cells (BMECs). Silencing EGFR using siRNA technology resulted in a marked decrease in the ability of C. neoformans to traverse the BMEC monolayer. Furthermore, C. neoformans infection also upregulates EGFR ligands, such as HB-EGF, in BMECs, thereby activating the EGFR signaling pathway. This activation involves the engagement of ADAM family metalloproteinases and the metalloprotease Mpr1 from C. neoformans. The findings of this study underscore the critical role of the host EGFR signaling pathway in the ability of C. neoformans to cross the BBB and highlight potential targets for developing new therapies for infectious meningitis.</p>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":" ","pages":"105540"},"PeriodicalIF":2.6,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248714","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":"Human Endogenous RetroViruses: The iceberg view.","authors":"Patrick Küry, Patrice N Marche","doi":"10.1016/j.micinf.2025.105530","DOIUrl":"10.1016/j.micinf.2025.105530","url":null,"abstract":"","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":" ","pages":"105530"},"PeriodicalIF":2.6,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248715","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":"Effects of sequential administration of phage cocktail, ciprofloxacin, and caspofungin on Staphylococcus aureus and Candida albicans dual-species biofilms.","authors":"Marta Gliźniewicz, Barbara Dołęgowska, Adrian Augustyniak, Rafał Rakoczy, Tomasz Kędzierski, Ewa Mijowska, Bartłomiej Grygorcewicz","doi":"10.1016/j.micinf.2025.105531","DOIUrl":"10.1016/j.micinf.2025.105531","url":null,"abstract":"<p><p>Polymicrobial biofilms, including inter-kingdom ones, represent another threat in the post-antibiotic era. Therefore, many alternative solutions are being investigated, including phage-antibiotic synergy (PAS), which may be more effective due to the differing mechanisms of action of drugs and phages. In this study, we evaluated how different sequences of administering a bacteriophage cocktail, ciprofloxacin, and caspofungin affect the eradication of S. aureus and C. albicans in vitro (planktonic culture and in biofilms). In liquid culture, the phage → caspofungin → ciprofloxacin treatment completely eradicated both organisms. In biofilms, the most effective regimens were either the simultaneous application of all three agents or phages + ciprofloxacin followed by caspofungin. Therefore, the sequence of administration of drugs and phages is a key factor in achieving effective therapy and revealing the most synergistic combinations.</p>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":" ","pages":"105531"},"PeriodicalIF":2.6,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199603","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":"Protection conferred by mucosal novel bivalent Klebsiella pneumoniae vaccine immunization associates with presence of lung CD4+ TRM","authors":"BiXia Liu ,&nbsp;YaRu Gu ,&nbsp;YangXue Ou ,&nbsp;LuXuan Liu ,&nbsp;WenHao Wang ,&nbsp;JinRui Zhou ,&nbsp;Ying Wang ,&nbsp;YeXiang Du ,&nbsp;Jing Xie ,&nbsp;Yuan Liu ,&nbsp;Rui Zhang ,&nbsp;QianFei Zuo ,&nbsp;Bin Wang","doi":"10.1016/j.micinf.2025.105483","DOIUrl":"10.1016/j.micinf.2025.105483","url":null,"abstract":"<div><div><em>Klebsiella pneumoniae</em> is the principal cause of hospital-acquired infection with a high morbidity and mortality in immunocompromised individuals, yet no vaccine is approved. Here, we developed a novel bivalent subunit vaccine for the prevention of <em>K. pneumoniae</em> infection based on the outer membrane protein GlnH and the fimbriae protein FimA. The survival rate of immunized mice was significantly increased compared to that of unimmunized mice, while the bacterial burden, weight loss, and lung pathology were drastically reduced. Furthermore, vaccine-elicited CD4⁺ T_RM cells were observed in lung tissues and appeared to play a critical role in vaccine efficacy. Transcriptomic analysis of total lung tissues from mice treated by FTY720 (S1PR1 inhibitor that blocks lymphocyte egress from secondary lymphoid structures) showed that cell activation, cytokine secretion and enhancement of the killing ability of neutrophils were related to the mechanism of protection against <em>K. pneumoniae</em> infection. These findings indicate that GlnH and FimA are effective candidate bivalent vaccine to fight <em>K. pneumoniae</em> infection.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 4","pages":"Article 105483"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625409","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":"Metabolic profile and disordered glycerophospholipid metabolism in recurrent vulvovaginal candidiasis","authors":"Jing Chen ,&nbsp;Yaoling Wang ,&nbsp;Xinyi Chen ,&nbsp;Fangfang Di,&nbsp;Guanghua Wang,&nbsp;Runjie Zhang,&nbsp;Jin Qiu","doi":"10.1016/j.micinf.2025.105504","DOIUrl":"10.1016/j.micinf.2025.105504","url":null,"abstract":"<div><div>Recurrent vulvovaginal candidiasis (RVVC) takes a toll not only on women's reproductive system but also on patients' life quality. The pathogenesis is still not fully understood. This study sought to explore metabolic profile of vaginal discharge from RVVC patients using non-targeted metabolomics and investigate potential bioactive functions of metabolites. The metabolic spectrum of RVVC patients was remarkably distinguished from healthy control and VVC patients. 324 metabolites with significant difference were detected in RVVC compared with control group, of which 239 were upregulated and 85 were downregulated. Moreover, compared with VVC, RVVC had a total of 67 significantly different metabolites including 43 upregulated metabolites and 24 downregulated metabolites. KEGG pathway analysis showed that Glycerophospholipid (GPL) metabolic pathway and PPAR signaling pathway were significantly changed in RVVC and the metabolites enriched into GPL metabolic pathway including LysoPC(18:1(11Z)), LysoPC(20:3(5Z,8Z,11Z)), PC(16:0/20:2(11Z,14Z)), PC(18:1(11Z)/18:1(9Z)) and PE(22:2(13Z,16Z)/18:3(9Z,12Z,15Z)) were significantly changed in RVVC patients and of high AUC values. In addition, the highest increased LysoPS(18:1(9Z)/0:0) in RVVC was demonstrated to not only inhibit the proliferation and migration of vaginal epithelial cells but also promote apoptosis. Molecular docking which showed strongly bind between LysoPS(18:1(9Z)/0:0) and PPAR-γ lead to a hypothesis that LysoPS(18:1(9Z)/0:0) may have an influence on RVVC through PPAR signaling pathway. Our findings provide new perspectives in understanding the pathogenesis of RVVC.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 4","pages":"Article 105504"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144031505","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":"Porcine alveolar macrophages and nasal epithelial cells internalize porcine epidemic diarrhea virus (PEDV) but do not support its replication in vitro","authors":"Carlos López-Figueroa ,&nbsp;Noelia Carmona-Vicente ,&nbsp;Esmeralda Cano ,&nbsp;Núria Navarro ,&nbsp;Cristina Risco ,&nbsp;Joan Repullés ,&nbsp;Joaquim Segalés ,&nbsp;Júlia Vergara-Alert","doi":"10.1016/j.micinf.2025.105500","DOIUrl":"10.1016/j.micinf.2025.105500","url":null,"abstract":"<div><div>Porcine epidemic diarrhea virus (PEDV) primarily targets enterocytes subsequent to fecal-oral exposure, resulting in severe gastrointestinal disease in neonatal piglets. However, recent evidence suggests potential alternative PEDV entry and replication routes via the respiratory tract. The present study delved into the possibility of an alternative pathway for PEDV infection in porcine alveolar macrophages (PAMs), 3D4/21 cells (3D4), and nasal turbinate epithelial cells, focusing on the inherent innate antiviral and anti-inflammatory immune responses to a cell-adapted non-S INDEL USA PEDV strain. CCL-81 cells were used as positive controls of infection, while non-infected CCL-81, PAMs, and 3D4 cells served as negative controls. Quantification of the viral load in cells and supernatants (SN) was carried out at multiple hours post-inoculation (hpi; 0, 6, 12, 24, 48, 72, and 96 hpi) using RT-qPCR, while infectious virus titers were assessed through TCID₅₀/ml on cell cultures and immunofluorescence (IF) staining. PEDV capture and internalization were examined using IF at 24 and 48 hpi, alongside the evaluation of the presence of viral particles and ultrastructural changes using transmission electron microscopy (TEM). Proinflammatory and antiviral cytokine levels in SN were measured using ELISA and Luminex. In both PAMs and 3D4 cells, PEDV RNA levels peaked at 12 hpi in cells and SN, then declined gradually without significant differences between cell types. Only few PAMs and 3D4 cells tested positive for PEDV IF, with no increase in positive cells between 24 and 48 hpi. TEM did not reveal viral particles or changes in cell organelles, and no proinflammatory or antiviral cytokine expression was detected in either cell type of macrophage cells. In parallel, nasal turbinate organoids (NTOs), cultivated as 2D monolayer and at an air-liquid interface (ALI), were exposed to PEDV, with RT-qPCR and IF conducted at 24 hpi. Despite the cultivation technique used, similar levels of PEDV RNA were detected in both the cells and the SN, with positive results observed for PEDV IF. Overall, while PAMs, 3D4 cells and nasal epithelium can capture and internalize PEDV, they do not support viral replication or trigger an antiviral or anti-inflammatory responses.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 4","pages":"Article 105500"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780473","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":"Copyright page Elsevier","authors":"","doi":"10.1016/S1286-4579(25)00067-X","DOIUrl":"10.1016/S1286-4579(25)00067-X","url":null,"abstract":"","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 4","pages":"Article 105535"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144221854","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":"Immunostimulatory effects of Hsp70 fragments-modified DCs: A computational and experimental study in HIV vaccine design","authors":"Elahe Akbari ,&nbsp;Alireza Milani ,&nbsp;Parisa Moradi Pordanjani ,&nbsp;Masoud Seyedinkhorasani ,&nbsp;Elnaz Agi ,&nbsp;Azam Bolhassani","doi":"10.1016/j.micinf.2025.105480","DOIUrl":"10.1016/j.micinf.2025.105480","url":null,"abstract":"<div><h3>Background</h3><div>Dendritic cells (DCs) loaded with HIV-1 antigens have been explored as a promising therapeutic approach to overcome HIV-1 infection. Heat shock proteins (Hsps) can improve cross-presentation of linked antigens by DCs. Our aim was a comprehensive <em>in silico</em>, <em>in vitro</em>, and <em>in vivo</em> evaluation of fusion proteins comprising the <em>N</em>- and C-terminal regions of Hsp70 (<em>i.e.,</em> NT-Hsp70 and CT-Hsp70) as an adjuvant linked to HIV-1 Nef antigen in development of DCs-based vaccine candidates.</div></div><div><h3>Methods</h3><div>Computational analyses of the NT-Hsp70-Nef and CT-Hsp70-Nef fusion constructs were performed, and their structural features and docking ability with toll-like or endocytic receptors were evaluated. The effectiveness of DCs loaded with the fusion proteins in eliciting immunity was assessed in mice. Cytokine secretion levels from splenocytes exposed to single-cycle replicable (SCR) HIV-1 were also measured <em>in vitro</em>.</div></div><div><h3>Results</h3><div>The DCs pulsed with the fusion constructs induced robust cellular and humoral immune responses in mice and infected splenocytes. The CT-Hsp70 region showed better docking scores with immune receptors and superior adjuvanticity for inducing Nef-specific immune responses (Th1 and CTL activity) compared to the NT-Hsp70 region in DC-based immunization.</div></div><div><h3>Conclusions</h3><div>The CT-Hsp70-Nef protein demonstrated promising results in both computational and experimental analyses compared to the NT-Hsp70-Nef protein.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 4","pages":"Article 105480"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432538","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":"TRIM32 positively regulates c-di-GMP-Induced type I interferon signaling pathway in Listeria monocytogenes infection","authors":"Yaya Pian ,&nbsp;Xuan OuYang","doi":"10.1016/j.micinf.2025.105499","DOIUrl":"10.1016/j.micinf.2025.105499","url":null,"abstract":"<div><div><em>Listeria monocytogenes</em> (<em>Lm</em>) poses a significant threat to human health. TRIM32, an E3 ubiquitin ligase, plays a critical role in regulating immune responses to pathogen infections. Previous studies have shown that TRIM32 deficiency significantly impairs IFN-β production. In this study, we demonstrate that TRIM32 enhances IFN-β release upon activation by cyclic di-GMP (c-di-GMP). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that TRIM32 deficiency upregulates genes associated with metabolic pathways while downregulating those involved in cytokine signaling and inflammatory responses. Western blot analysis further indicated a significant reduction in ERK and JNK phosphorylation in splenocytes and peritoneal macrophages, suggesting that TRIM32 modulates the MAPK signaling pathway. Additionally, the duration of p38, STAT, and TBK1 phosphorylation was shortened in bone marrow-derived macrophages. Collectively, these findings highlight the role of TRIM32 in enhancing the host immune response against <em>Lm</em> infection.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 4","pages":"Article 105499"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573463","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}