PLoS Pathogens最新文献

{"title":"Platelet-leucocyte interactions drive MMP-mediated tissue damage in tuberculosis.","authors":"Daniela E Kirwan, Deborah L W Chong, Oscar Gayoso, Jorge Coronel, Maria-Cristina Loader, Cesar A Ugarte-Gil, Lilia Cabrera, Ricardo C Medrano, Kirk A Taylor, Michael Emerson, Ivan Lozada-Requena, Julia Kutschenreuter, Mirko Zimic, Robert H Gilman, Jon S Friedland","doi":"10.1371/journal.ppat.1014205","DOIUrl":"https://doi.org/10.1371/journal.ppat.1014205","url":null,"abstract":"<p><p>Tuberculosis causes inflammation and excess matrix metalloproteinase (MMP) activity which lead to tissue damage and adverse patient outcomes. Platelets are emerging as key drivers of inflammation, and platelet-leucocyte aggregate formation via interactions between platelet P-selectin and monocyte PSGL-1 receptors may regulate tissue destruction in tuberculosis. First, a platelet-monocyte co-culture model was utilised to assess platelet-leucocyte interactions. We then examined M.tb-infected and control lymph node tissue using immunofluorescence microscopy. Finally, we investigated tuberculosis patients (TB, n = 17), healthy controls (HC, n = 14), and patients undergoing bronchoscopy subsequently classified as TB (n = 10) or respiratory symptomatic (RS, n = 14). Whole blood was collected to quantify platelet aggregation using light transmission aggregometry, and platelet-monocyte aggregates (PMA), platelet-neutrophil aggregates (PNA), and platelet receptor expression using flow cytometry. In M.tb-infected monocytes, addition of platelets significantly increased secretion of MMP-1 and MMP-10 and upregulated mmp1 gene expression 4.7-fold. MMP-1 secretion was also increased by addition of platelet-derived soluble factors, and by monocyte PSGL-1 receptor ligation. We observed abundant platelets in M.tb-infected lymph node tissue, localising to PSGL-1 receptors on monocytic cells, and this was not seen in M.tb-uninfected control tissue from patients with reactive hyperplasia or with lymphoma. Ex vivo platelet aggregation in response to stimulation with platelet agonist ADP (3µM, 10µM, and 30µM) was reduced in patients with TB versus HC. PMA were increased in TB and RS versus HC, while PNA were raised only in TB; platelet receptor expression was unchanged. Platelet P-selectin expression, PMA, and PNA correlated with each other but were independent of platelet expression of GPIIb/IIIa, indicating dissociation from thrombotic pathways. In summary, PSGL-1/P-selectin mediated platelet-leucocyte interactions drive inflammation and secretion of MMPs in pulmonary TB. This identifies platelets as important regulators of tissue-damaging inflammatory responses in tuberculosis. Targeting this pathway represents a potential host-directed therapeutic strategy in tuberculosis, and possibly in other lung diseases.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"22 5","pages":"e1014205"},"PeriodicalIF":4.9,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147876635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: An atypical F-type ATPase is necessary for the function of the antibody cleavage system MIB-MIP in mycoplasmas.","authors":"","doi":"10.1371/journal.ppat.1014203","DOIUrl":"https://doi.org/10.1371/journal.ppat.1014203","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1371/journal.ppat.1014043.].</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"22 5","pages":"e1014203"},"PeriodicalIF":4.9,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147876543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How post-translational modifications in pathogenic fungi inform pathogenesis and immune responses.","authors":"Satya Ranjan Sahu, Charles A Specht, Stuart M Levitz","doi":"10.1371/journal.ppat.1014162","DOIUrl":"10.1371/journal.ppat.1014162","url":null,"abstract":"","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"22 5","pages":"e1014162"},"PeriodicalIF":4.9,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13155678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147857533","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}

{"title":"SPRY domains encode ubiquitin ligase specificity for ZAP and RIG-I.","authors":"Ibrahim Syed, Sheng Chen, David J Peeler, Paul F McKay, Marco A Briones-Orta, Jennifer A Bohn, Robin J Shattock, Daniel Gonçalves-Carneiro","doi":"10.1371/journal.ppat.1014195","DOIUrl":"https://doi.org/10.1371/journal.ppat.1014195","url":null,"abstract":"<p><p>Innate immune sensors rely on ubiquitin ligases to calibrate antiviral responses, yet the rules governing substrate recognition by SPRY-containing ligases remain poorly defined. Here, we establish a large-scale structure-based screening pipeline using AlphaFold to systematically predict interactions between human nucleic acid sensors and SPRY-containing proteins. Our approach uncovered novel transient or degradation-sensitive interactions that are typically missed by proteomic methods, including a labile TRIM58-OAS1 complex. We show that SPRY domains dictate substrate specificity: TRIM25 preferentially engages ZAP, whereas Riplet favors RIG-I. Domain-swapping experiments demonstrated that SPRY domains are sufficient to reprogram ligase specificity and antiviral activity. Phylogenetic and structural analyses revealed that TRIM25 and Riplet evolved from a common ancestor but diverged in coiled-coil architecture and oligomeric state, while retaining conserved substrate preferences. Residue-level modeling identified hypervariable SPRY loops as critical determinants of recognition, a prediction validated by targeted mutagenesis of the TRIM25-ZAP interface. Finally, we show that distinct SPRY-containing ligases surveil self-amplifying RNA (saRNA) vaccines: Riplet-RIG-I primarily responds when RNA is delivered by lipofection, whereas TRIM25-ZAP is engaged upon lipid nanoparticle delivery, with functional consequences for vaccine expression. Together, these findings demonstrate that SPRY domains encode recognition logic for ubiquitin ligases, that AlphaFold enables discovery of otherwise hidden interactions and that these principles have direct implications for RNA-based therapeutics.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"22 5","pages":"e1014195"},"PeriodicalIF":4.9,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147857514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Wolbachia-induced Cytoplasmic Incompatibility drives epigenetic and maternally-influenced post-embryonic defects.","authors":"Claire Perez, Jillian Porter, Brandt Warecki, William Sullivan","doi":"10.1371/journal.ppat.1014180","DOIUrl":"10.1371/journal.ppat.1014180","url":null,"abstract":"<p><p>A common form of Wolbachia-induced manipulation of host reproduction is Cytoplasmic Incompatibility (CI). In CI, Wolbachia modification of sperm results in pronounced defects in paternal chromosome condensation, replication, and segregation during the first mitotic division. Recent studies in D. simulans demonstrate that CI also induces independent and distinct later developmental defects resulting in high rates of mitotic errors during the mid-blastula transition and larval lethality. Here we show that in D. melanogaster, embryos derived from CI crosses experienced significant mitotic defects during gastrulation and increased larval lethality, both of which were eliminated in the progeny of Rescue crosses (both sexes infected). Examination of CI using females from 13 genetically distinct wild-type lines of the Drosophila Genetic Reference Panel (DGRP) revealed significant variation in the strength of the CI-induced lethality. Early embryonic pre-hatching and late larval lethal phases were uncorrelated, suggesting distinct factors influence the extent of the two lethal phases. Additionally, 3rd instar larvae and adults derived from D. melanogaster CI crosses exhibited locomotor defects that were also eliminated in Rescue crosses. These studies support a model in which Wolbachia effects on the sperm chromatin produce delayed developmental and locomotor defects, suggesting the involvement of epigenetic mechanisms. Support for this idea comes from our finding that levels of the heritable chromatin mark H3K27me1 are significantly elevated in CI-derived embryos. We conclude that the full measure of CI strength should take into account pre- and post-hatching lethality as well as locomotor defects. Together our findings suggest that the strength of these CI-induced phenotypes is governed at least in part by epigenetics and the maternal genetic background.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"22 5","pages":"e1014180"},"PeriodicalIF":4.9,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13152123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147845040","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}

{"title":"An IL-1, IL-17, and IL-22 cytokine circuit controls vulvovaginal candidiasis independently of estrogen.","authors":"Bianca M Coleman, Melissa E Cook, Md Robin Khan, Amanda K Vogel, Anthony J Wells, Jian Miao, Shachi P Vyas, Tiffany C Taylor, Felix E Y Aggor, Nicole O Ponde, Ipsita Dey, Henry Zou, Eldin Jašarević, Brian M Peters, Sarah L Gaffen","doi":"10.1371/journal.ppat.1014202","DOIUrl":"10.1371/journal.ppat.1014202","url":null,"abstract":"<p><p>Vulvovaginal candidiasis (VVC) affects >75% of women, with considerable morbidity and high medical cost burden. While Type 17 cytokines (IL-17, IL-22) are critical for oral and dermal immunity to C. albicans, their role in VVC has been less clear. Th17 gene signatures are potently upregulated in VVC, yet impairment of individual Th17 components (IL-17A, IL-17R subunits, IL-22) does not worsen disease. Rather, estrogen activity is tightly linked to VVC, leading to a paradigm that hormonal pathways, rather than immune defense, dominate susceptibility. Here, we reveal a previously unappreciated role for IL-1/Type 17 in VVC that operates independently of estrogenic hormones. In contrast to mice lacking IL-17A, IL-17RA, IL-22, or IL-22R individually, mice lacking IL-17RA and IL-22RA1 together (Il17raIl22ra1-/-) exhibited high fungal loads and exacerbated tissue damage and inflammation during estrogen-induced VVC. In human vulvar epithelial cells, IL-17 and IL-22 drive synergistic signaling. IL-1R signaling but surprisingly not IL-23 was upstream of this response. Il17raIl22ra1-/- mice expressed high IL-1β yet did not control disease, indicating that IL-1 is upstream but not downstream of Type 17 responses. Unexpectedly, Type 17-dependent control occurred in the absence of exogenous estrogen administration and persisted even when estrus was prevented by progesterone treatment. Collectively, these data indicate that susceptibility to VVC is driven not only by estrogen sensitization but through combinatorial loss of IL-17 and IL-22.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"22 5","pages":"e1014202"},"PeriodicalIF":4.9,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147844690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Weak selection and stochastic processes limit the emergence of antigenic variants during household transmission of influenza A viruses.","authors":"Hunter J Ries, Joseph Lalli, Kelsey R Florek, Shari Barlow, Maureen Goss, Richard Griesser, Tonya Danz, Amra Uzicanin, Jonathan Temte, Thomas C Friedrich","doi":"10.1371/journal.ppat.1013689","DOIUrl":"10.1371/journal.ppat.1013689","url":null,"abstract":"<p><p>Influenza viruses undergo antigenic drift, the gradual accumulation of mutations that cause antigenic changes in the viral surface proteins hemagglutinin (HA) and neuraminidase (NA). Although selection for antigenic variants is detectable on the global scale, the processes by which antigenic variants are generated and selected in individual hosts remain unclear. It has been hypothesized that selection for antigenic variants may occur during the establishment of a new infection, rather than over time in a single host. Here, we leveraged a large household cohort study to assess whether selection was detectable between acutely infected hosts. We investigated influenza A virus evolution using specimens from 384 children and household contacts with RT-PCR-confirmed influenza A infection, representing infections with A(H1N1)pdm09 and A(H3N2) viruses from 2017-19. In agreement with prior studies, we found that acute infections involved weak purifying selection across the viral genome. In addition, we identified 40 transmission events occurring in 31 households. During transmission, evolution between hosts was characterized by tight transmission bottlenecks and weak purifying selection. We found variability in the strength and direction of selection on antigenic regions of HA, but no clear evidence for selection of antigenic variants during transmission. Together, our results indicate that stochastic processes and weak natural selection dominate most acute influenza A virus infections and transmission events, and that selection of antigenic variants during transmission between acutely infected hosts is likely to be exceedingly rare.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"22 5","pages":"e1013689"},"PeriodicalIF":4.9,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147844969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tracking fungal pathogens on cancer: Oncomicrobes or opportunistic bystanders?","authors":"Rosana Alves, Wouter Van Genechten, Patrick Van Dijck","doi":"10.1371/journal.ppat.1014179","DOIUrl":"10.1371/journal.ppat.1014179","url":null,"abstract":"","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"22 5","pages":"e1014179"},"PeriodicalIF":4.9,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13152125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147845023","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}

{"title":"Globodera pallida virulence on major potato resistance has a common genetic basis across Western Europe.","authors":"Arno S Schaveling, Leidy van Rijt, Yoonseon Do, Nike Soffree, Daan Langendoen, Hilde Room, André Machado Bertran, Margien Raven, Sebastiaan P van Kessel, Evelyn Y J van Heese, Stefan J S van de Ruitenbeek, Casper C van Schaik, Sebastian Kiewnick, Geert Smant, Mark G Sterken","doi":"10.1371/journal.ppat.1014201","DOIUrl":"10.1371/journal.ppat.1014201","url":null,"abstract":"<p><p>The potato cyst nematode Globodera pallida poses a major threat to potato production in Western Europe. Current management strategies largely depend on the use of potato varieties carrying the genetic resistance GpaVvrn. However, reports from multiple West-European countries indicate a steady rise in virulence against GpaVvrn-containing potato varieties, raising serious concerns about G. pallida control. Although recent studies have resolved the genetic basis of virulence in two Dutch G. pallida populations, it remains unclear how conserved this genetic adaptation is in populations from different regions. To investigate this, we first selected eight Dutch G. pallida populations on the GpaVvrn-containing potato variety Seresta and confirmed a previously identified virulence locus. Second, by analysing the allele frequencies of four virulence-associated SNPs in Dutch, British, and French GpaVvrn-selected G. pallida populations, we found that the same allele is consistently selected by GpaVvrn across Western Europe. Third, we analysed the propagation of eight G. pallida populations on 26 GpaVvrn-containing potato varieties and showed that a population's allele frequency of a single SNP (T173N) accurately reflects its reproduction on GpaVvrn. Fourth, we developed an allele-specific quantitative PCR (AS-qPCR) assay to determine a population's alternative allele frequency (AAF) of T173N and showed that AS-qPCR-based AAFs reliably indicate virulence levels on GpaVvrn in Dutch and German G. pallida populations. Together, these findings suggest that a common allele is consistently selected by GpaVvrn in populations from different regions across Western Europe. The AS-qPCR assay developed in this study provides a practical tool to estimate G. pallida virulence on GpaVvrn in the field, enabling field-tailored and sustainable resistance management strategies for farmers.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"22 5","pages":"e1014201"},"PeriodicalIF":4.9,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147844938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The stage-specific regulation and role of root-knot nematode SWEET genes.","authors":"M Willow H Maxwell, Bharat Rohilla, Jasper Chippendale, Chris A Bell","doi":"10.1371/journal.ppat.1014161","DOIUrl":"10.1371/journal.ppat.1014161","url":null,"abstract":"<p><p>The root-knot nematode Meloidogyne incognita is a globally significant plant parasite that causes substantial crop losses. While pre-parasitic juveniles rely on innate energy reserves, later life stages acquire nutrients from host plants through specialized feeding structures. SWEET (Sugars Will Eventually be Exported Transporter) genes exhibit a conserved sugar transporting ability across all kingdoms of life, yet their function in plant-parasitic nematodes remains underexplored. Here, we functionally characterise the SWEET gene family in M. incognita, revealing their critical and stage-specific roles in nematode development and parasitism. We demonstrate that Mi-SWEETs segregate into two functional groups: those that facilitate mobility and invasion in motile juveniles (Mi-SWEET2, 4) and those support nutrient uptake during feeding (Mi-SWEET3, 5, 7). Although temporally distinct, all SWEET genes localise to the intestine, suggesting a conserved role in mediating sugar flux. Knockdown of Mi-SWEET2 and Mi-SWEET4 reduced root invasion, while silencing Mi-SWEET3, 5, and 7 impaired post-invasion growth, highlighting the varied roles of this large gene family across different life stages. Yeast complementation assays revealed distinct substrate preferences among Mi-SWEETs, aligning with the metabolic needs of different life stages. The transcription factor HBL1, a key regulator of nematode dietary responses, was found to control the expression of Mi-SWEET3 and is itself regulated through interaction with the post-transcriptional regulatory microRNA let-7. Our findings provide new insights into the metabolic adaptations and energy utilisation of plant-parasitic nematodes and outline a microRNA - transcription factor - target gene regulatory network. These findings have broader relevance given the fundamental importance of the regulation of resource transportation in plant-pathogen interactions.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"22 5","pages":"e1014161"},"PeriodicalIF":4.9,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13148671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147844962","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}