PLoS Pathogens最新文献_第9页

Cross-kingdom dialogs in the gut: Integrating bacterial pathogens, helminths, and microbiota interactions for immune homeostasis. 肠道中的跨界对话：整合细菌病原体、蠕虫和微生物群的相互作用以实现免疫稳态。

IF 4.9 1区医学

PLoS Pathogens Pub Date : 2025-09-11 eCollection Date: 2025-09-01 DOI: 10.1371/journal.ppat.1013494

Suhui Hu, Zhenzhen Liu, Wenchao Yan, Rongxian Guo

{"title":"Cross-kingdom dialogs in the gut: Integrating bacterial pathogens, helminths, and microbiota interactions for immune homeostasis.","authors":"Suhui Hu, Zhenzhen Liu, Wenchao Yan, Rongxian Guo","doi":"10.1371/journal.ppat.1013494","DOIUrl":"10.1371/journal.ppat.1013494","url":null,"abstract":"The interactions between bacterial pathogens, helminths, and commensal microbiota in the gut form a complex ecological network that profoundly impacts host immunity and health. Pathogens employ strategies such as type VI secretion systems (T6SS) and inflammation induction to evade colonization resistance, disrupt microbial balance, and establish self-benefit ecological niches. These interactions involve competition with commensal bacteria and helminths, which play a critical role in maintaining gut homeostasis by occupying ecological niches, competing for nutrient, and supporting the mucus barrier. Meanwhile, helminths can modulate commensal bacterial gene expression, metabolic activity, and survival by secreting excretory-secretory products. In addition, by inducing a Th2 immune response, helminths can enhance the intestinal mucosal barrier, alter the gut microbiota composition, and thereby inhibit bacterial pathogen colonization. Interestingly, helminths and pathogens can exhibit synergistic or competitive relationships. For instance, Ascaris lumbricoides may provide a survival niche for Vibrio cholerae, while helminths can also indirectly inhibit pathogenic bacteria through immune modulation. These intricate interactions influence gut microbial composition, digestion, and immune function, and are closely associated with diseases. Future research should focus on elucidating the molecular mechanisms underlying these interactions. Understanding the interactions between pathogens, helminths, and commensal microbiota not only provides novel insights into maintaining host immune homeostasis but also establishes a theoretical foundation for future development of gut health intervention strategies.","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 9","pages":"e1013494"},"PeriodicalIF":4.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12425192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145042116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Rapid clearance of inducible HIV-1 proviruses after initiation of antiretroviral therapy. 开始抗逆转录病毒治疗后可诱导的HIV-1原病毒的快速清除。

IF 4.9 1区医学

PLoS Pathogens Pub Date : 2025-09-11 eCollection Date: 2025-09-01 DOI: 10.1371/journal.ppat.1013466

Maria C Puertas, Lucía Bailón, Víctor Urrea, Maria C García-Guerrero, Yovaninna Alarcón-Soto, Angel Rivero, Beatriz Mothe, José Moltó, Javier Martinez-Picado

{"title":"Rapid clearance of inducible HIV-1 proviruses after initiation of antiretroviral therapy.","authors":"Maria C Puertas, Lucía Bailón, Víctor Urrea, Maria C García-Guerrero, Yovaninna Alarcón-Soto, Angel Rivero, Beatriz Mothe, José Moltó, Javier Martinez-Picado","doi":"10.1371/journal.ppat.1013466","DOIUrl":"10.1371/journal.ppat.1013466","url":null,"abstract":"Despite its efficacy, antiretroviral therapy (ART) is not curative, and HIV-1 rebound occurs whenever treatment is interrupted. The viral reservoir in latently infected cells is the source of the infection resurgence, making it crucial to understand when and how this reservoir is established so that it can be targeted more effectively. In this study, we evaluated the decay dynamics of proviral DNA in 40 ART-naive people initiating dolutegravir-based treatment and compared these dynamics to the decay kinetics of inducible proviruses, as measured using the VIP-SPOT assay. Intensive sampling during the first month, followed by regular sampling up to 48 weeks, enabled us to outline the biphasic decay dynamics of different fractions of the viral reservoir. Our results show that the first decay phase of inducible proviruses is significantly faster than that of total HIV-1 DNA (2.6 days versus 5.1 weeks), indicating that selective pressure on this specific fraction of proviruses is particularly effective during the first days after ART initiation. These findings suggest that therapeutic interventions aimed at impacting the viral reservoir by boosting the immune response targeting the inducible fraction should be implemented at the time of, or immediately before, treatment initiation.","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 9","pages":"e1013466"},"PeriodicalIF":4.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12449031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145042076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction: Polyamine biosynthesis and eIF5A hypusination are modulated by the DNA tumor virus KSHV and promote KSHV viral infection. 更正：DNA肿瘤病毒KSHV调节多胺生物合成和eIF5A的作用，促进KSHV病毒感染。

IF 4.9 1区医学

PLoS Pathogens Pub Date : 2025-09-11 eCollection Date: 2025-09-01 DOI: 10.1371/journal.ppat.1013496

Guillaume N Fiches, Zhenyu Wu, Dawei Zhou, Ayan Biswas, Tai-Wei Li, Weili Kong, Maxime Jean, Netty G Santoso, Jian Zhu

引用次数: 0

Antifungal persistence: Clinical relevance and mechanisms. 抗真菌持久性：临床相关性和机制。

IF 4.9 1区医学

PLoS Pathogens Pub Date : 2025-09-11 eCollection Date: 2025-09-01 DOI: 10.1371/journal.ppat.1013456

Rui Wang, Jingnan Lv, Liang Chen, Yanan Zhao, Hong Du

引用次数: 0

HIV-1 Tat favors the multiplication of Mycobacterium tuberculosis and Toxoplasma by inhibiting clathrin-mediated endocytosis and autophagy. HIV-1通过抑制网格蛋白介导的内吞和自噬，有利于结核分枝杆菌和弓形虫的增殖。

IF 4.9 1区医学

PLoS Pathogens Pub Date : 2025-09-11 eCollection Date: 2025-09-01 DOI: 10.1371/journal.ppat.1013183

Aurélie Rivault, Audrey Bernut, Myriam Ben-Neji, Magali Abrantes, Maxime Jansen, Sylvaine Huc-Brandt, Sébastien Besteiro, Yann Bordat, Mai Nguyen-Chi, Nelly Audemard, Margaux Mesleard-Roux, David Perrais, Olivier Neyrolles, Geanncarlo Lugo-Villarino, Christel Vérollet, Lucile Espert, Bruno Beaumelle

{"title":"HIV-1 Tat favors the multiplication of Mycobacterium tuberculosis and Toxoplasma by inhibiting clathrin-mediated endocytosis and autophagy.","authors":"Aurélie Rivault, Audrey Bernut, Myriam Ben-Neji, Magali Abrantes, Maxime Jansen, Sylvaine Huc-Brandt, Sébastien Besteiro, Yann Bordat, Mai Nguyen-Chi, Nelly Audemard, Margaux Mesleard-Roux, David Perrais, Olivier Neyrolles, Geanncarlo Lugo-Villarino, Christel Vérollet, Lucile Espert, Bruno Beaumelle","doi":"10.1371/journal.ppat.1013183","DOIUrl":"10.1371/journal.ppat.1013183","url":null,"abstract":"HIV-1 and Mycobacterium tuberculosis (Mtb) coinfections are a major public health problem but are not well characterized. HIV-1 Tat is secreted by infected cells, generating nanomolar concentrations of Tat in the sera of people living with HIV. Circulating Tat enters cells, binds to PI(4,5)P2 then undergoes palmitoylation, thereby becoming resident on this phosphoinositide. Here, we found that Tat favors the multiplication of Mtb in macrophages. Moreover, Tat renders zebrafish larvae more sensitive to mycobacterial infection. We found that Tat binding to PI(4,5)P2 and palmitoylation enable Tat to inhibit the recruitment of the AP-2 adaptor, thereby inhibiting clathrin-mediated endocytosis and in turn autophagy. This inhibition prevents the degradation of intracellular pathogens such as Mtb and opsonized Toxoplasma gondii, but also of lipid droplets, thereby facilitating the access of these pathogens to lipids. We thus identified a mechanism enabling HIV Tat to favor the multiplication of intracellular pathogens such as Mtb.","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 9","pages":"e1013183"},"PeriodicalIF":4.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12445553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145042048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dendritic cells and HIV transmission: roles and subsets of antigen-presenting cells in the human anogenital tract. 树突状细胞和HIV传播：抗原呈递细胞在人类肛门生殖道中的作用和亚群。

IF 4.9 1区医学

PLoS Pathogens Pub Date : 2025-09-10 eCollection Date: 2025-09-01 DOI: 10.1371/journal.ppat.1013490

Daniel J Buffa, Thomas R O'Neil, Erica E Vine, Lara Sarkawt, Freja A Warner van Dijk, Oscar A Dong, Najla Nasr, Anthony L Cunningham, Kirstie M Bertram, Andrew N Harman

{"title":"Dendritic cells and HIV transmission: roles and subsets of antigen-presenting cells in the human anogenital tract.","authors":"Daniel J Buffa, Thomas R O'Neil, Erica E Vine, Lara Sarkawt, Freja A Warner van Dijk, Oscar A Dong, Najla Nasr, Anthony L Cunningham, Kirstie M Bertram, Andrew N Harman","doi":"10.1371/journal.ppat.1013490","DOIUrl":"10.1371/journal.ppat.1013490","url":null,"abstract":"Dendritic cells (DCs) are potent antigen-presenting cells and play a key role in facilitating the sexual transmission of HIV, functioning as a delivery system responsible for trafficking the virus from exposed barrier sites to their key target cells, CD4 T cells. Although the role of DCs in HIV transmission is well established, the recent advent of high-parameter, single-cell detection technologies, coupled with improved cell isolation techniques, has led to the rapid reclassification of the DC landscape, particularly within human barrier tissues. The identification of new subsets introduces the challenge of incorporating previously understood transmission principles with new, cell-specific, functional nuances to identify the key DCs responsible for facilitating HIV infection. This review explores the history of research linking DCs with HIV transmission as well as our understanding of how HIV manipulates DC biology to achieve this purpose. Furthermore, it provides an up-to-date understanding of the antigen-presenting cell landscape within human anogenital tissues and how each subset contributes to sexual transmission. Uncovering the cells and biological processes responsible for the sexual transmission of HIV is a fundamental step in the pursuit of an HIV vaccine and better prophylaxis to block infection.","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 9","pages":"e1013490"},"PeriodicalIF":4.9,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12422496/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145034132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The dimorphic fungus Talaromyces marneffei: An opportunistic killer in Southeast Asia. 二形真菌马尔尼菲塔芳菌：东南亚的机会主义杀手。

IF 4.9 1区医学

PLoS Pathogens Pub Date : 2025-09-10 eCollection Date: 2025-09-01 DOI: 10.1371/journal.ppat.1013444

Lottie Brown, Alex Andrianopoulos, Patrick C Y Woo, Thuy Le

引用次数: 0

CK2 derived from brain microvascular endothelial cells induces astrocyte inflammatory response in Escherichia coli-induced meningitis. 脑微血管内皮细胞来源的CK2诱导大肠杆菌诱导的脑膜炎的星形胶质细胞炎症反应。

IF 4.9 1区医学

PLoS Pathogens Pub Date : 2025-09-10 eCollection Date: 2025-09-01 DOI: 10.1371/journal.ppat.1013464

Dong Huo, Ruicheng Yang, Jiyang Fu, Jiaqi Chen, Chen Tan, Huanchun Chen, Xiangru Wang

{"title":"CK2 derived from brain microvascular endothelial cells induces astrocyte inflammatory response in Escherichia coli-induced meningitis.","authors":"Dong Huo, Ruicheng Yang, Jiyang Fu, Jiaqi Chen, Chen Tan, Huanchun Chen, Xiangru Wang","doi":"10.1371/journal.ppat.1013464","DOIUrl":"10.1371/journal.ppat.1013464","url":null,"abstract":"Neuroinflammation within the central nervous system (CNS) is recognized as a critical pathological process in meningitic Escherichia coli (E. coli) infection, leading to severe neurodegenerative disorders and long-term sequelae. Astrocyte reactivity plays a pivotal role in driving the neuroinflammatory cascade in response to pathological stimuli from peripheral sources or other cellular components of the CNS. The involvement of astrocyte reactivity in the inflammatory process induced by bacterial infection within the CNS warrants further investigation. In this study, we observed an astrocyte reaction likely mediated by brain microvascular endothelial cells (BMEC) during meningitic E. coli infection in both a mouse model and a BMEC-astrocyte coculture system. Through label-free quantitative proteomics analysis of the BMEC secretome, we identified CK2 as a potential trigger for astrocyte reactivity. Inhibition of CK2 attenuated the reaction of hippocampal astrocytes in E. coli meningitis. Furthermore, we demonstrated that CK2 enhances NF-κB activation via its interaction with myosin 9, thereby increasing astrocyte reactivity and the inflammatory response both in vivo and in vitro. By conditionally knocking out CK2β in microvessel, we blocked CK2 secretion, resulting in reduced astrocyte reactivity and neuroinflammation during the early stages of infection. Compared to wild-type mice, CK2βVas-/- mice exhibited a significantly higher survival rate. Collectively, our findings highlight the essential role of endothelial-glial communication mediated by CK2 interaction with myosin 9 in activating the downstream NF-κB pathway, contributing to astrocyte reactivity and neuroinflammation. These results provide novel insights into the treatment of CNS inflammation caused by bacterial blood-borne infections.","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 9","pages":"e1013464"},"PeriodicalIF":4.9,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12422478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145034143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Salmonella phage shock protein system is required for defense against host antimicrobial peptides. 沙门氏菌噬菌体休克蛋白系统是防御宿主抗菌肽所必需的。

IF 4.9 1区医学

PLoS Pathogens Pub Date : 2025-09-09 eCollection Date: 2025-09-01 DOI: 10.1371/journal.ppat.1013132

Marie-Ange Massicotte, Aline A Fiebig, Andrei Bogza, Brian K Coombes

{"title":"The Salmonella phage shock protein system is required for defense against host antimicrobial peptides.","authors":"Marie-Ange Massicotte, Aline A Fiebig, Andrei Bogza, Brian K Coombes","doi":"10.1371/journal.ppat.1013132","DOIUrl":"10.1371/journal.ppat.1013132","url":null,"abstract":"Macrophages are professional phagocytes that play a major role in engulfing and eliminating invading pathogens. Some intracellular pathogens, such as Salmonella enterica serovar Typhimurium, exploit macrophages as niches for their replication, which requires precise and dynamic modulation of bacterial gene expression in order to resist the hostile intracellular environment. Here, we present a comprehensive analysis of the global transcriptome of S. Typhimurium across four stages of infection of primary macrophages. Our results revealed a profound change in early-stage gene expression dominated by pathways linked to metabolic processes required for Salmonella adaptation to the proinflammatory conditions of the macrophage. We identified the phage shock protein (Psp) system to be highly expressed in intracellular S. Typhimurium, with sustained high expression over the course of infection. We determined that the Psp system is regulated by the virulence-associated two-component system SsrA-SsrB, which coordinates its expression with critical bacterial functions required for immune evasion and intracellular survival. Functional assays demonstrated that the Psp system mediates resistance to host antimicrobial peptides, including cathelicidin-related antimicrobial peptide (CRAMP), which we demonstrate supports bacterial persistence in host tissues and survival within macrophages. Our findings establish the Psp system as a new and critical adaptive mechanism for evading host immune defenses and highlight the utility of temporal transcriptomics in unraveling the genetic strategies employed by S. Typhimurium during macrophage infection.","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 9","pages":"e1013132"},"PeriodicalIF":4.9,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12440182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Assembly of the mitochondrial outer membrane module of the trypanosomal tripartite attachment complex. 锥虫三方附着复合体的线粒体外膜组件组装。

IF 4.9 1区医学

PLoS Pathogens Pub Date : 2025-09-09 eCollection Date: 2025-09-01 DOI: 10.1371/journal.ppat.1013506

Philip Stettler, Salome Aeschlimann, Bernd Schimanski, André Schneider

{"title":"Assembly of the mitochondrial outer membrane module of the trypanosomal tripartite attachment complex.","authors":"Philip Stettler, Salome Aeschlimann, Bernd Schimanski, André Schneider","doi":"10.1371/journal.ppat.1013506","DOIUrl":"10.1371/journal.ppat.1013506","url":null,"abstract":"The parasitic protozoan Trypanosoma brucei has a single mitochondrial nucleoid, anchored to the basal body of the flagellum via the tripartite attachment complex (TAC). The detergent-insoluble TAC is essential for mitochondrial genome segregation during cytokinesis. The TAC assembles de novo in a directed way from the probasal body towards the kDNA. However, the OM TAC module which is composed of five subunits, has previously been suspected to follow more complicated assembly pathways. Here, we identified four detergent-soluble OM TAC module subcomplexes that we assign to two classes. One class contains an oligomeric TAC40 complex that according to AlphaFold contains 6-8 subunits, as well as two subcomplexes of different sizes comprising TAC40, TAC42, and TAC60. The second class consists of a single complex composed of TAC65 and pATOM36. We show that the two subcomplex classes form independently and accumulate upon impairment of TAC assembly. The expression of an N-terminally truncated TAC60 variant causes the accumulation of the larger TAC40/TAC42/TAC60 complex and blocks completion of OM TAC module assembly. This suggests the following assembly pathway: i) TAC40 oligomerizes, ii) TAC42 and TAC60 bind the TAC40 oligomer forming two discrete larger intermediates, where iii) the larger subcomplex merges with the pATOM36/TAC65 subcomplex subsequently forming the OM TAC module.","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 9","pages":"e1013506"},"PeriodicalIF":4.9,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12440218/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0