Infection and Immunity最新文献

{"title":"Carbon dioxide regulates <i>Mycobacterium tuberculosis</i> PhoPR signaling and virulence.","authors":"Shelby J Dechow, Rajni Goyal, Benjamin K Johnson, Elizabeth R Haiderer, Robert B Abramovitch","doi":"10.1128/iai.00568-24","DOIUrl":"10.1128/iai.00568-24","url":null,"abstract":"<p><p>The <i>Mycobacterium tuberculosis</i> (Mtb) two-component regulatory system PhoPR is implicated in pH sensing within the macrophage because it is strongly induced by acidic pH both <i>in vitro</i> and the macrophage phagosome. The carbonic anhydrase (CA) inhibitor ethoxzolamide inhibits PhoPR signaling supporting the hypothesis that CO₂ may also play a role in regulating PhoPR. Here, we show that increasing CO₂ concentration induces PhoPR signaling, at both pH 7.0 and pH 5.7. At acidic pH 5.7, a normally strong inducer of PhoPR signaling, increasing CO₂ from 0.5% to 5% further induces the pathway, showing CO₂ acts synergistically with acidic pH to induce the PhoPR regulon. Based on these findings, we propose that PhoPR functions as a CO₂ sensor. Mtb has three CA (CanA, CanB, and CanC), and using CRISPR interference knockdowns and gene deletion mutants, we assessed which CAs regulate PhoPR signaling and macrophage survival. We first examined if CA played a role in Mtb pathogenesis and observed that CanB was required for survival in macrophages, where the knockdown strain had ~1-log reduction in survival. To further define the interplay of CO₂ and Mtb signaling, we conducted transcriptional profiling experiments at varying pH and CO₂ concentrations. As hypothesized, we observed that the induction of PhoPR at acidic pH is dependent on CO₂ concentration, with a subset of core PhoPR regulon genes dependent on both 5% CO₂ and acidic pH for their induction, including expression of the ESX-1 secretion system. Transcriptional profiling also revealed core CO₂-responsive genes that were differentially expressed independently of the PhoPR regulon or the acidic pH-inducible regulon. Notably, genes regulated by a second two-component regulatory system, TrcRS, are associated with adaptation to changes in CO₂.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0056824"},"PeriodicalIF":2.9,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Article of Significant Interest in This Issue.","authors":"","doi":"10.1128/iai.00105-25","DOIUrl":"10.1128/iai.00105-25","url":null,"abstract":"","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":"93 3","pages":"e0010525"},"PeriodicalIF":2.9,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11917524/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zinc-limited <i>Mycobacterium tuberculosis</i> stimulate distinct responses in macrophages compared with standard zinc-replete bacteria.","authors":"Endrei Marcantonio, Allexa D Burger, Kelly H Chang, Fukun W Hoffmann, Yuanyuan Fu, Vedbar S Khadka, Benoit J Smagghe, Youping Deng, Peter R Hoffmann, Sladjana Prisic","doi":"10.1128/iai.00578-24","DOIUrl":"10.1128/iai.00578-24","url":null,"abstract":"<p><p>Tuberculosis (TB) is notoriously difficult to treat, likely due to the complex host-pathogen interactions driven by pathogen heterogeneity. An understudied area of TB pathogenesis is host responses to <i>Mycobacterium tuberculosis</i> bacteria (Mtb) that are limited in zinc ions. This distinct population resides in necrotic granulomas and sputum and could be the key player in tuberculosis pathogenicity. In this study, we tested the hypothesis that macrophages differentiate between Mtb grown under zinc limitation or in the standard zinc-replete medium. Using several macrophage infection models, such as murine RAW 264.7 and murine bone marrow-derived macrophages (BMDMs), as well as human THP-1-derived macrophages, we show that macrophages infected with zinc-limited Mtb have increased bacterial burden compared with macrophages infected with zinc-replete Mtb. We further demonstrate that macrophage infection with zinc-limited Mtb trigger higher production of reactive oxygen species (ROS) and cause more macrophage death. Furthermore, the increased ROS production is linked to the increased phagocytosis of zinc-limited Mtb, whereas cell death is not. Finally, transcriptional analysis of RAW 264.7 macrophages demonstrates that macrophages have more robust pro-inflammatory responses when infected with zinc-limited Mtb than zinc-replete Mtb. Together, our findings suggest that Mtb's access to zinc affects their interaction with macrophages and that zinc-limited Mtb may be influencing TB progression. Therefore, zinc availability in bacterial growth medium should be considered in TB drug and vaccine developments.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0057824"},"PeriodicalIF":2.9,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Orientia tsutsugamushi</i> alters the intranuclear balance of cullin-1 and c-MYC to inhibit apoptosis.","authors":"Paige E Allen, Haley E Adcox, Thomas E Siff, Sarika Gupta, Jason R Hunt, Jason A Carlyon","doi":"10.1128/iai.00559-24","DOIUrl":"10.1128/iai.00559-24","url":null,"abstract":"<p><p>Cullin-1 (Cul1), a cullin-RING ubiquitin ligase component, represses c-MYC activity in the nucleus. <i>Orientia tsutsugamushi</i> causes the potentially fatal rickettsiosis, scrub typhus. The obligate intracellular bacterium encodes an arsenal of ankyrin repeat-containing effectors (Anks), many of which carry a eukaryotic-like F-box motif that binds Cul1. <i>O. tsutsugamushi</i> reduces Cul1 levels in the nucleus. This phenomenon is not due to an alteration in Cul1 neddylation but is bacterial burden- and protein synthesis-dependent. Five of the 11 Anks capable of binding Cul1 (Ank1, Ank5, Ank6, Ank9, Ank17) sequester it in the cytoplasm when each is ectopically expressed. Ank1 and Ank6 proteins with alanine substitutions in their F-boxes that render them unable to bind Cul1 cannot exclude Cul1 from the nucleus. Coincident with the reduction of Cul1 in the nuclei of <i>Orientia</i>-infected cells, c-MYC nuclear levels are elevated, and Cul1 target genes are differentially expressed. Several of these genes regulate apoptosis. The resistance of <i>O. tsutsugamushi</i>-infected cells to staurosporine-induced apoptosis is recapitulated in uninfected cells expressing Ank1 or Ank6 but not alanine-substituted versions thereof that cannot bind Cul1. Other F-box-containing Anks that cannot bind or exclude Cul1 from the nucleus also fail to confer resistance to apoptosis. Overall, <i>O. tsutsugamushi</i> modulates the Cul1:c-MYC intranuclear balance as an anti-apoptotic strategy that is functionally linked to a subset of its F-box-containing Anks.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0055924"},"PeriodicalIF":2.9,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Chlamydia</i> plasmid-encoded protein Pgp2 is a replication initiator with a unique β-hairpin necessary for iteron-binding and plasmid replication.","authors":"Danny Wan, Matthew Pan, Guangming Zhong, Huizhou Fan","doi":"10.1128/iai.00602-24","DOIUrl":"10.1128/iai.00602-24","url":null,"abstract":"<p><p>The virulence plasmid of the obligate intracellular bacterium <i>Chlamydia</i> encodes eight proteins. Among these, Pgp3 is crucial for pathogenicity, and Pgp4 functions as a transcriptional regulator of both plasmid and chromosomal genes. The remaining proteins, Pgp1, Pgp5, Pgp6, Pgp7, and Pgp8, are predicted to play various roles in plasmid replication or maintenance based on their amino acid sequences. However, the function of Pgp2 remains unknown, even though it is required for transformation. In this study, we utilized AlphaFold to predict the three-dimensional (3-D) structure of <i>Chlamydia trachomatis</i> Pgp2. Despite a lack of apparent sequence homology, the AlphaFold structure exhibited high similarity to experimentally determined structures of several plasmid replication initiators. Notably, Pgp2 features a unique β-hairpin motif near the DNA-binding domain, absent in other plasmid replication initiators with overall 3-D structures similar to Pgp2. This β-hairpin motif is also present in AlphaFold models of Pgp2s across all 13 <i>Chlamydia</i> species. To assess its significance, we engineered a plasmid lacking the 11 amino acids constituting the β-hairpin motif in <i>C. trachomatis</i> Pgp2. Although this deletion did not alter the overall structure of Pgp2, the mutated plasmid failed to transform plasmid-free <i>C. trachomatis</i>. These findings reveal that Pgp2 is a plasmid replication initiator, with the β-hairpin motif playing a critical role in binding to its cognate iteron sequences in the replication origin of the chlamydial plasmid.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0060224"},"PeriodicalIF":2.9,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human Factor H and anti-Neisserial surface protein A (NspA) antibodies compete for overlapping binding sites on meningococcal NspA.","authors":"Dhaarini Raghunathan, Susie Sohee Lim, Gregory R Moe, Peter T Beernink","doi":"10.1128/iai.00339-24","DOIUrl":"10.1128/iai.00339-24","url":null,"abstract":"<p><p>Neisserial surface protein A (NspA) is a small, conserved outer membrane protein that has been investigated as a vaccine antigen against meningococcal disease. After NspA had been tested in humans, this antigen was discovered to recruit the human complement regulator Factor H (FH). Previous studies in transgenic mice showed that human FH decreased the protective antibody responses to NspA. The purpose of the present study was to map the binding sites for human FH and anti-NspA antibodies. We found that an anti-NspA monoclonal antibody (mAb), AL-12, inhibits binding of FH to NspA by enzyme-linked immunosorbent assay (ELISA). Based on this result, we tested the roles of the 10 charged residues on the external loops of NspA in binding these two molecules by site-specific mutagenesis and binding experiments. Through ELISA and surface plasmon resonance experiments, we show that three aspartate (D) residues, D77 on loop 2 and D113 and D118 on loop 3, are important for binding human FH. Further, residues D113 and D118, as well as lysine 79 and arginine 109, are involved in binding mAb AL-12, which binds to a conformational epitope. The results have implications for strategies to increase NspA immunogenicity by decreasing binding to human FH, as has been done with other antigens that recruit this complement regulator.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0033924"},"PeriodicalIF":2.9,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estrogen prevented gingival barrier injury from <i>Porphyromonas gingivalis</i> lipopolysaccharide.","authors":"Fangting Huang, Zhifei Su, Fangjie Zhou, Yajie Wu, Jiyao Li, Biao Ren","doi":"10.1128/iai.00410-24","DOIUrl":"10.1128/iai.00410-24","url":null,"abstract":"<p><p>The postmenopausal population usually suffers from more severe periodontal disease than non-menopausal women due to the decrease and low levels of estrogen, especially β-estradiol (E2). While additional estrogen therapy can effectively relieve alveolar bone resorption, this suggests that estrogen has played an important role in the development of periodontitis. The integrity of the gingival epithelial barrier plays a key role in protecting gingival tissue from inflammatory injury caused by pathogens. However, it remains unclear whether estrogen can maintain the integrity of the gingival epithelial barrier to reduce inflammatory injury. Here, using an infection model established with <i>Porphyromonas gingivalis</i> lipopolysaccharide (LPS) in human gingival epithelial cells (hGECs) and ovariectomized or Sham mice, we assessed the protective effect of estrogen on the gingival barrier using qPCR, western blotting, immunohistochemistry, and transcriptome analysis. The results showed that estrogen restored epithelial barrier function to inhibit <i>P. gingivalis</i>-LPS invasion and further downregulate the inflammatory reaction (<i>P</i> < 0.05) by upregulating expressions of tight junction proteins (such as JAM1 and OCLN) at mRNA and protein levels in both hGECs and ovariectomized or Sham mice (<i>P</i> < 0.05). Estrogen also protected against alveolar bone resorption and preserved barrier integrity in both ovariectomized and Sham mice (<i>P</i> < 0.05). In conclusion, E2 prevented the progression of gingival epithelial barrier damage and inflammation induced by <i>P. gingivalis</i>-LPS by increasing the expression of tight junction proteins. The protective effect of estrogen on gingival epithelial barrier injury highlighted its potential application in treating periodontitis and inflammatory diseases involving epithelial barrier dysfunction.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0041024"},"PeriodicalIF":2.9,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11918251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proinflammatory synergy between protease and superantigen streptococcal pyogenic exotoxins.","authors":"Anders F Johnson, Summer D Bushman, Doris L LaRock, Juan Manuel Díaz, John K McCormick, Christopher N LaRock","doi":"10.1128/iai.00405-24","DOIUrl":"10.1128/iai.00405-24","url":null,"abstract":"<p><p>Streptococcal pyogenic exotoxins (Spe proteins) secreted by <i>Streptococcus pyogenes</i> (group A <i>Streptococcus</i>, GAS) are responsible for scarlet fever and streptococcal toxic shock syndrome. Most Spes are superantigens that cause excessive inflammation by activating large numbers of T cells. However, Streptococcal pyogenic exotoxin B (SpeB) is an exception, which is pro-inflammatory through its protease activity. Prior work shows that SpeB has the potential to cleave bacterial proteins. If cleavage of superantigens results in their inactivation, this gives the possibility that these two classes of exotoxins work at cross-purposes. We examined SpeB cleavage of the 11 major GAS superantigens and found that lability was not specific to structure, conservation, or, when compared to orthologous superantigens from <i>Staphylococcus aureus</i>, species of origin. We further show that rather than strictly antagonizing superantigen activity through degradation, SpeB can synergistically enhance superantigen-induced inflammation. For SpeB-labile superantigens, such as SmeZ, this is limited due to degradation, but for protease-resistant superantigens like SpeA, activity remains synergistic even at high protease concentrations. These findings suggest two modes by which proteases like SpeB may post-translationally regulate superantigens: positively, as a force amplifier that cooperatively increases inflammation, and negatively, through degradation that could act as a rheostat-like mechanism to limit excessive immune activation. Both mechanisms may contribute to the pathogenesis of GAS and other superantigen-producing pathogens.<b>IMPORTANCE</b><i>Streptococcus pyogenes</i> produces both superantigen and protease virulence factors to subvert host immunity. However, its major protease is highly promiscuous and would potentially limit superantigen activity through its degradation. We profile the sensitivity of the streptococcal superantigens to degradation by the protease SpeB, providing evidence that many are highly resistant. Furthermore, we show that these important toxins can have synergistic proinflammatory activity. This provides insight into diseases like scarlet fever and toxic shock syndrome caused by these toxins and suggests anti-inflammatories that may be therapeutically useful.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0040524"},"PeriodicalIF":2.9,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895496/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell wall glycosyltransferase of <i>Streptococcus mutans</i> impacts its dissemination to murine organs.","authors":"Tomomi Hashizume-Takizawa, Taiki Ando, Ayaka Urakawa, Kazuhiro Aoki, Hedenobu Senpuku","doi":"10.1128/iai.00097-24","DOIUrl":"10.1128/iai.00097-24","url":null,"abstract":"<p><p><i>Streptococcus mutans</i>, a cariogenic bacterium in humans, is associated with systemic disorders. Its cariogenic factors include glucosyltransferases (GTFs) and the glycosyltransferase rhamnose-glucose polysaccharide I (RgpI), which is involved in cell wall synthesis. However, the potential roles of these enzymes in systemic disorders remain unclear. We constructed a luciferase-tagged <i>S. mutans</i> UA159 mutant strain that lacked <i>rgpI</i> to explore the involvement of this enzyme in the systemic pathogenicity of <i>S. mutans</i>. We also employed the luciferase-tagged <i>S. mutans</i> UA159 variant, which exhibited reduced GTF production and therefore had a low glucan synthesis ability. We intravenously inoculated these luciferase-tagged mutants and parent strains into 12-week-old male BALB/c mice to evaluate their distribution to organs. Strong luminescence was noted in the spleen and kidneys, indicating that <i>S. mutans</i> was disseminated to these organs. Several organs collected from mice inoculated with the luciferase-tagged parent strain emitted a signal, and inflammatory cytokine production was detected in the blood. The luminescence intensity was lower in the kidneys of mice challenged with the mutant strain, which has a low glucan synthesis ability. Conversely, challenge with the <i>rgpI</i> deletion mutant strain resulted in the lowest number of luminescent organs, with a lower intensity and attenuated inflammation. Furthermore, all the mice inoculated with the <i>rgpI</i> deletion mutant strain survived, whereas not all the mice inoculated with the parent strain survived. Collectively, these results suggest that RgpI is involved in the systemic pathogenicity of <i>S. mutans</i> UA159.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0009724"},"PeriodicalIF":2.9,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunostimulatory effects of <i>Streptococcus sanguinis</i> extracellular membrane vesicles protect oral gingival epithelial cells from periodontal pathobiont damage.","authors":"Emily Helliwell, Isabella Rauch, Tim Nice, Justin Merritt, Jens Kreth","doi":"10.1128/iai.00535-24","DOIUrl":"10.1128/iai.00535-24","url":null,"abstract":"<p><p>The commensal <i>Streptococcus sanguinis</i> is highly prevalent in the oral cavity and characterized for its ability to inhibit growth of oral pathogens. Like many other cell types, streptococci produce extracellular membrane vesicles (EMVs), which contain specific molecular cargo and facilitate interactions with host cells. We previously demonstrated that EMVs from <i>S. sanguinis</i> are internalized by gingival epithelial cells (GECs) without causing cell death. Our aim is to characterize the effects of vesicles on eukaryotic cells. Microscopy studies of gingival epithelial cells inoculated with EMVs from wild-type and specific deletion mutants show differential uptake, with decreased uptake of ΔSSA1099 EMVs and increased uptake of ΔSSA1882 EMVs relative to SK36 EMVs. However, EMVs from wild-type and deletion mutants showed similar patterns in cytokine and chemokine secretion. Transcriptomic analysis of gingival epithelial cells inoculated with SK36 EMVs showed a downregulation of genes implicated in apoptosis as well as interferon signaling, while showing an upregulation of genes involved in cytokine production. Gelatin zymography results show that SK36 EMVs have a contrasting result on production of MMP2/9; MMP2 production is decreased while MMP9 is increased by 48 hours post-inoculation (hpi). Dual-inoculation studies demonstrate that prior internalization of <i>S. sanguinis</i> EMVs protects gingival epithelial cells from exposure to pathobiont <i>Porphyromonas gingivalis</i> outer membrane vesicles (OMVs), preventing dissociation and cell death. Our overall findings suggest that <i>S. sanguinis</i> EMVs trigger an immune response on gingival epithelial cells; however, this response suggests inhibition of some immune signaling pathways. Our results highlight an important role in commensalism, in which a microbe induces an immune response but avoids damage to host cells, thus discouraging infection by pathobionts.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0053524"},"PeriodicalIF":2.9,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}