Stephanie Michael, Nicholas Liotta, Tongyi Fei, Matthew L. Bendall, Douglas F. Nixon, Nicholas Dopkins
{"title":"Endogenous retroelement expression in modeled airway epithelial repair","authors":"Stephanie Michael, Nicholas Liotta, Tongyi Fei, Matthew L. Bendall, Douglas F. Nixon, Nicholas Dopkins","doi":"10.1016/j.micinf.2024.105465","DOIUrl":"10.1016/j.micinf.2024.105465","url":null,"abstract":"<div><div>Cystic fibrosis (CF) is an autosomal recessive genetic disorder characterized by impairment of the CF transmembrane conductance regulator (CFTR) via gene mutation. CFTR is expressed at the cellular membrane of epithelial cells and functions as an anion pump which maintains water and salt ion homeostasis. In pulmonary airways of CF patients, pathogens such as <em>P. aeruginosa</em> and subsequent uncontrolled inflammation damage the human airway epithelial cells (HAECs) and can be life-threatening. We previously identified that inhibiting endogenous retroelement (ERE) reverse transcriptase can hamper the inflammatory response to bacterial flagella in THP-1 cells. Here, we investigate how ERE expression is sensitive to HAEC repair and toll-like receptor 5 (TLR5) activation, a primary mechanism by which inflammation impacts disease outcome. Our results demonstrate that several human endogenous retroviruses (HERVs) and long interspersed nuclear elements (LINEs) fluctuate throughout the various stages of repair and that TLR5 activation further influences ERE expression. By considering the impact of the most common CF mutation F508del/F508del on ERE expression in unwounded HAECs, we also found that two specific EREs, L1FLnI_2p23.1c and HERVH_10p12.33, were downregulated in CF-derived HAECs. Collectively, we show that ERE expression in HAECs is sensitive to certain modalities reflective of CF pathogenesis, and specific EREs may be indicative of CF disease state and pathogenesis.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 5","pages":"Article 105465"},"PeriodicalIF":2.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142837495","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":"27 5","pages":"Article 105530"},"PeriodicalIF":2.7,"publicationDate":"2025-07-01","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":"Endogenous retroviruses in neurodevelopmental, psychotic and cognitive disorders","authors":"Urs Meyer , Iris Katharina Penner","doi":"10.1016/j.micinf.2025.105479","DOIUrl":"10.1016/j.micinf.2025.105479","url":null,"abstract":"<div><div>Endogenous retroviruses (ERVs) are inherited retroviral genomic elements that integrated into the mammalian genome through germline infections and insertions during evolution. Human ERVs (HERVs) comprise approximately 8 % of the human genome and are increasingly recognized to be involved in the etiology and pathophysiology of numerous brain disorders. In this narrative review, we summarize the existing evidence linking abnormal HERV expression to neurodevelopmental and psychosis-related disorders and discuss how these retroviral elements may contribute to the heterogeneity in clinical outcomes. We also review the findings suggesting that aberrant HERV expression contribute to late-onset cognitive disorders with neurodegenerative components, such as Alzheimer's disease (AD) and other forms of dementia. The evidence implicating abnormal HERV expression in neurodevelopmental, psychotic, and cognitive disorders is manifold and stems from diverse research fields, including human post-mortem brain studies, serological investigations, gene expression analyses, and clinical trials with HERV-specific pharmacological compounds. The recent establishment and use of animal models offer a complementary experimental platform that will help establish causal relationships and identify specific disease pathways affected by abnormal HERV expression. Yet, significant gaps persist in understanding the role of HERVs in neurodevelopmental, psychotic, and cognitive disorders, particularly concerning the specificity and stability of abnormal HERV expression in these conditions. Addressing these questions appears crucial for optimizing the potential benefits of therapeutic interventions aimed at targeting abnormal HERV expression across the broad spectrum of HERV-associated disorders of the central nervous system.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 5","pages":"Article 105479"},"PeriodicalIF":2.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365055","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":"HERV-W ENV transcription in B cells predicting symptomatic COVID-19 and risk for long COVID can express a full-length protein despite stop codon in mRNA from chromosome X via a ribosome readthrough","authors":"Joanna Brunel , Julien Paganini , Melissa Galloux , Benjamin Charvet , Hervé Perron","doi":"10.1016/j.micinf.2024.105431","DOIUrl":"10.1016/j.micinf.2024.105431","url":null,"abstract":"<div><div>The human genome comprises 8 % of endogenous retroviruses (HERVs). Though HERVS contribute to physiological functions, copies retained pathogenic potential. The HERV-W ENV protein was shown expressed in patients with worse COVID-19 symptoms and post-COVID syndrome. A significant detection of the mRNA encoding HERV-W ENV from patients with COVID-19 in B cells from RNAseq reads obtained from peripheral blond mononuclear cells. This data stratified with increased COVID-19 symptoms or with post-acute sequelae of COVID-19 (long COVID) after 3 months. The HERV-W <em>ENV-U3R</em> RNA was confirmed to display the best alignment with chromosome X ERVWE2 locus. However, a stop codon precluding its translation was re-addressed after recent understandings of ribosome readthrough mechanisms. Experimental results evidenced that this HERV gene can effectively express a full-length protein in the presence of molecules allowing translation via a readthrough mechanism at the ribosome level. Results not only confirm HERV-W <em>ENV</em> RNA origin in these patients but show for the first time how a defective HERV copy can be translated into a complete protein when specific factors make it possible at the ribosome level. The present proof of concept now requires further studies to identify the factors involved in this newly understood mechanism, following SARS-CoV-2 exposure.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 5","pages":"Article 105431"},"PeriodicalIF":2.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142469725","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}
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
{"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}
Marta Gliźniewicz, Barbara Dołęgowska, Adrian Augustyniak, Rafał Rakoczy, Tomasz Kędzierski, Ewa Mijowska, Bartłomiej Grygorcewicz
{"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}
BiXia Liu , YaRu Gu , YangXue Ou , LuXuan Liu , WenHao Wang , JinRui Zhou , Ying Wang , YeXiang Du , Jing Xie , Yuan Liu , Rui Zhang , QianFei Zuo , Bin Wang
{"title":"Protection conferred by mucosal novel bivalent Klebsiella pneumoniae vaccine immunization associates with presence of lung CD4+ TRM","authors":"BiXia Liu , YaRu Gu , YangXue Ou , LuXuan Liu , WenHao Wang , JinRui Zhou , Ying Wang , YeXiang Du , Jing Xie , Yuan Liu , Rui Zhang , QianFei Zuo , 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<sup>+</sup> T<sub>RM</sub> 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}
Jing Chen , Yaoling Wang , Xinyi Chen , Fangfang Di, Guanghua Wang, Runjie Zhang, Jin Qiu
{"title":"Metabolic profile and disordered glycerophospholipid metabolism in recurrent vulvovaginal candidiasis","authors":"Jing Chen , Yaoling Wang , Xinyi Chen , Fangfang Di, Guanghua Wang, Runjie Zhang, 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}