Infection and Immunity最新文献

{"title":"The host GTPase Dynamin 2 modulates apical junction structure to control cell-to-cell spread of <i>Listeria monocytogenes</i>.","authors":"Serena Tijoriwalla, Thiloma Liyanage, Thilina U B Herath, Nicole Lee, Attika Rehman, Antonella Gianfelice, Keith Ireton","doi":"10.1128/iai.00136-24","DOIUrl":"10.1128/iai.00136-24","url":null,"abstract":"<p><p>The food-borne pathogen <i>Listeria monocytogenes</i> uses actin-based motility to generate plasma membrane protrusions that mediate the spread of bacteria between host cells. In polarized epithelial cells, efficient protrusion formation by <i>L. monocytogenes</i> requires the secreted bacterial protein InlC, which binds to a carboxyl-terminal Src homology 3 (SH3) domain in the human scaffolding protein Tuba. This interaction antagonizes Tuba, thereby diminishing cortical tension at the apical junctional complex and enhancing <i>L. monocytogenes</i> protrusion formation and spread. Tuba contains five SH3 domains apart from the domain that interacts with InlC. Here, we show that human GTPase Dynamin 2 associates with two SH3 domains in the amino-terminus of Tuba and acts together with this scaffolding protein to control the spread of <i>L. monocytogenes</i>. Genetic or pharmacological inhibition of Dynamin 2 or knockdown of Tuba each restored normal protrusion formation and spread to a bacterial strain deleted for the <i>inlC</i> gene (∆<i>inlC</i>). Dynamin 2 localized to apical junctions in uninfected human cells and protrusions in cells infected with <i>L. monocytogenes</i>. Localization of Dynamin 2 to junctions and protrusions depended on Tuba. Knockdown of Dynamin 2 or Tuba diminished junctional linearity, indicating a role for these proteins in controlling cortical tension. Infection with <i>L. monocytogenes</i> induced InlC-dependent displacement of Dynamin 2 from junctions, suggesting a possible mechanism of antagonism of this GTPase. Collectively, our results show that Dynamin 2 cooperates with Tuba to promote intercellular tension that restricts the spread of ∆<i>inlC Listeria</i>. By expressing InlC, wild-type <i>L. monocytogenes</i> overcomes this restriction.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0013624"},"PeriodicalIF":2.9,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11475654/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916559","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":"The impact of butyrate on group B <i>Streptococcus</i>-induced intestinal barrier disruption.","authors":"Kristen Dominguez, Alexia N Pearah, April K Lindon, Leigh-Anne M Worthington, Rico R Carter, Nichol John-Lewis Edwards, Thao T B Ho, Sophie E Darch, Tara M Randis","doi":"10.1128/iai.00200-24","DOIUrl":"10.1128/iai.00200-24","url":null,"abstract":"<p><p>Group B Streptococcus (<i>Streptococcus agalactiae</i>; GBS) is a leading cause of neonatal sepsis worldwide. As a pathobiont of the intestinal tract, it is capable of translocating across barriers leading to invasive disease. Neonatal susceptibility to invasive disease stems from immature intestinal barriers. GBS intestinal colonization induces major transcriptomic changes in the intestinal epithelium related to barrier function. Butyrate, a microbial metabolite produced by fermentation of dietary fiber, bolsters intestinal barrier function against enteric pathogens, and these effects can be transferred <i>in utero</i> via the placenta to the developing fetus. Our aim was to determine if butyrate mitigates GBS disruption of intestinal barriers. We used human intestinal epithelial cell (IEC) lines to evaluate the impact of butyrate on GBS-induced cell death and GBS adhesion and invasion. IECs and human fetal tissue-derived enteroids were used to evaluate monolayer permeability. We evaluated the impact of maternal butyrate treatment (mButyrate) using our established mouse model of neonatal GBS intestinal colonization and late-onset sepsis. We found that butyrate reduces GBS-induced cell death, GBS invasion, monolayer permeability, and translocation <i>in vitro</i>. In mice, mButyrate decreases GBS intestinal burden in offspring. Our results demonstrate the importance of bacterial metabolites, such as butyrate, in their potential to bolster epithelial barrier function and mitigate neonatal sepsis risk.IMPORTANCEGroup B <i>Streptococcus</i> (GBS) is a leading cause of neonatal morbidity and mortality. It is a commensal of the intestines that can translocate across barriers leading to sepsis in vulnerable newborns. With the rise in antibiotic-resistant strains and no licensed vaccine, there is an urgent need for preventative strategies. Butyrate, a short-chain fatty acid metabolized in the gut, enhances barrier function against pathogens. Importantly, butyrate is transferred <i>in utero</i>, conferring these benefits to infants. Here, we demonstrate that butyrate reduces GBS colonization and epithelial invasion. These effects were not microbiome-driven, suggesting butyrate directly impacts epithelial barrier function. Our results highlight the potential impact of maternal dietary metabolites, like butyrate, as a strategy to mitigate neonatal sepsis risk.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0020024"},"PeriodicalIF":2.9,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11475668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916560","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":"Protective innate immunity against <i>Pneumocystis</i> does not require Stat6-dependent macrophage polarization.","authors":"T Mousso, S J Pollock, P C Inzerillo, F Gigliotti, T W Wright","doi":"10.1128/iai.00222-24","DOIUrl":"10.1128/iai.00222-24","url":null,"abstract":"<p><p><i>Pneumocystis</i> species are respiratory fungal pathogens that cause life-threatening opportunistic infections in immunocompromised hosts. <i>Pneumocystis</i> typically evade pulmonary innate immunity but are efficiently eradicated by a functional adaptive immune response. FVB/NJ mice are unique in that they display protective alveolar macrophage-dependent innate immunity against <i>Pneumocystis</i>, and remain resistant to infection even in the absence of CD4⁺ T lymphocyte function. FVB/NJ alveolar macrophages (AMs) were found to display an M2-biased phenotype at baseline, which was potentiated after stimulation with <i>Pneumocystis</i>, suggesting that macrophage polarization may dictate the outcome of the <i>Pneumocystis</i>-macrophage interaction. To determine whether Stat6, a key global regulator of M2 polarization, was required for FVB/NJ innate immunity, FVB Stat6^-/- mice were generated. FVB Stat6-deficient AMs were markedly impaired in their ability to polarize to an M2 phenotype when stimulated with Th2 cytokines. However, FVB Stat6^-/- mice remained highly resistant to infection, indicating that Stat6 signaling is dispensable for innate FVB/NJ resistance. Despite the loss of Stat6 signaling, primary AMs from FVB Stat6^-/- mice maintained baseline expression of M2 markers, and also strongly upregulated M2-associated genes following direct stimulation with <i>Pneumocystis</i>. Additional FVB/NJ knockout strains were generated, but only FVB MerTK^-/- mice showed a marginally increased susceptibility to <i>Pneumocystis</i> infection. Together, these findings demonstrate that effective FVB/NJ innate immunity against <i>Pneumocystis</i> does not require Stat6 signaling and suggest that alternative pathways regulate M2 bias and macrophage-mediated innate resistance in FVB/NJ mice.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0022224"},"PeriodicalIF":2.9,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11475768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987856","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":"Articles of Significant Interest in This Issue.","authors":"","doi":"10.1128/iai.00437-24","DOIUrl":"https://doi.org/10.1128/iai.00437-24","url":null,"abstract":"","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":"92 10","pages":"e0043724"},"PeriodicalIF":2.9,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11481855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464293","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":"NLRP3 inflammasome inhibition decreases <i>Schistosomiasis japonica</i>-induced granulomatous inflammation and fibrosis in BALB/c mice.","authors":"Yaqi Lu, Jing Liu, Wangxian Tang, Heng Zhang","doi":"10.1128/iai.00055-24","DOIUrl":"10.1128/iai.00055-24","url":null,"abstract":"<p><p>To research the role of the NLRP3 inflammasome in <i>Schistosoma japonicum</i>-induced granuloma formation and liver fibrosis. In <i>in vivo</i> tests, BALB/c mice were used. shNLRP3 plasmid based on adeno-associated virus serotype 8 (AAV8-shNLRP3) was injected to block NLRP3 inflammasome via tail vein. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were detected to assess liver injury. H&E staining was used for routine histopathological assessment; Masson's trichrome staining was used to detect fibrous tissues and collagen fibers. Hepatic expression of NLRP3, procaspase-1, bioactive caspase-1, collagen-1, tissue inhibitor of metalloproteinases-1 (TIMP-1), and α-smooth muscle actin (α-SMA) were detected by western blot. Serum levels of IL-1β were detected by enzyme-linked immunosorbent assay (ELISA). The inflammatory cell infiltration and hepatic expression of IL-1β around the granuloma were detected by immunohistochemistry staining. Treatment of <i>S. japonicum</i> infected mice with AAV8-shNLRP3 significantly reduced the hepatic levels of bioactive caspase-1 and IL-1β, as well as circulating IL-1β concentrations, while reducing the amounts of myeloperoxidase (MPO) and F4/80 positive cells around the granuloma. Moreover, collagen deposition, TIMP-1, and α-SMA, which are markers of hepatic stellate cell (HSC) activation, were reduced around the liver granuloma. These findings highlight a therapeutic potential of AAV8-shNLRP3 in schistosomiasis cirrhosis.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0005524"},"PeriodicalIF":2.9,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11475658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999846","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>Akkermansia muciniphila</i> alleviates abdominal aortic aneurysms via restoring CITED2 activated by EPAS1.","authors":"Siqing Wang, Hang Shi, Yue Cheng, Lei Jiang, Yang Lou, Manish Kumar, Mingfei Sun, Xianze Shao, Xuan Zhao, Baichun Wang","doi":"10.1128/iai.00172-24","DOIUrl":"10.1128/iai.00172-24","url":null,"abstract":"<p><p>Abdominal aortic aneurysm (AAA) is a life-threatening cardiovascular disease that has been linked to gut microbiome dysbiosis. Therefore, this study aims to investigate the effects of <i>Akkermansia muciniphila</i> (<i>Am</i>) on AAA mice and the biomolecules involved. AAA mice were generated using angiotensin II (Ang II), and 16sRNA sequencing was used to identify an altered abundance of microbiota in the feces of AAA mice. Vascular smooth muscle cell (VSMC) markers and apoptosis, and macrophage infiltration in mouse aortic tissues were examined. The abundance of <i>Am</i> was reduced in AAA mouse feces, and endothelial PAS domain-containing protein 1 (EPAS1) was downregulated in AAA mice and VSMC induced with Ang II. <i>Am</i> delayed AAA progression in mice, which was blunted by knockdown of EPAS1. EPAS1 was bound to the Cbp/p300-interacting transactivator 2 (CITED2) promoter and promoted CITED2 transcription. CITED2 reduced VSMC apoptosis and delayed AAA progression. Moreover, EPAS1 inhibited macrophage inflammatory response by promoting CITED2 transcription. In conclusion, gut microbiome dysbiosis in AAA induces EPAS1-mediated dysregulation of CITED2 to promote macrophage inflammatory response and VSMC apoptosis.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0017224"},"PeriodicalIF":2.9,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11477905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142107026","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":"Eosinophils respond to, but are not essential for control of an acute <i>Salmonella enterica</i> serovar Typhimurium infection in mice.","authors":"Rachael D FitzPatrick, Jonathan R Noone, Richard A Cartwright, Dominique M Gatti, Tara P Brosschot, Jenna M Lane, Erik L Jensen, Isabella Kroker Kimber, Lisa A Reynolds","doi":"10.1128/iai.00325-24","DOIUrl":"10.1128/iai.00325-24","url":null,"abstract":"<p><p>Eosinophils are a highly abundant cell type in the gastrointestinal tract during homeostatic conditions, where they have recently been reported to take on an activated phenotype following colonization by the bacterial microbiota. To date, there have been few studies investigating whether eosinophils respond to infection with enteric bacterial pathogens and/or investigating the requirements for eosinophils for effective bacterial pathogen control. In this study, we investigated the response of eosinophils to an acute enteric infection of mice with the bacterial pathogen <i>Salmonella enterica</i> serovar Typhimurium. We also assessed whether eosinophil deficiency impacted <i>Salmonella</i> burdens in the intestinal tract or impacted the systemic dissemination of <i>Salmonella</i> following an oral infection of littermate wild-type BALB/cJ and eosinophil-deficient ΔdblGATA BALB/cJ mice. We found comparable <i>Salmonella</i> burdens in the intestinal tract of wild-type and eosinophil-deficient mice and no significant differences in the levels of <i>Salmonella</i> disseminating to systemic organs within 3 days of infection. Despite our evidence suggesting that eosinophils are not an essential cell type for controlling bacterial burdens in this acute infection setting, we found higher levels of eosinophils in gut-draining lymph nodes following infection, indicating that eosinophils do respond to <i>Salmonella</i> infection. Our data contribute to the growing evidence that eosinophils are responsive to bacterial stimuli, yet the influence of and requirements for eosinophils during bacterial infection appear to be highly context-dependent.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0032524"},"PeriodicalIF":2.9,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11475665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153921","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":"Molecular, structural, and functional characterization of delta subunit of T-complex protein-1 from <i>Leishmania donovani</i>.","authors":"Apeksha Anand, Gunjan Gautam, Gaurava Srivastava, Shailendra Yadav, Karthik Ramalingam, Mohammad Imran Siddiqi, Neena Goyal","doi":"10.1128/iai.00234-24","DOIUrl":"10.1128/iai.00234-24","url":null,"abstract":"<p><p>Chaperonins/Heat shock protein 60 are ubiquitous multimeric protein complexes that assist in the folding of partially and/or misfolded proteins using metabolic energy into their native stage. The eukaryotic group II chaperonin, also referred as T-complex protein-1 ring complex (TRiC)/T-complex protein-1 (TCP1)/chaperonin containing T-complex protein (CCT), contains 8-9 paralogous subunits, arranged in each of the two rings of hetero-oligomeric complex. In <i>Leishmania</i>, till date, only one subunit, LdTCP1γ, has been well studied. Here, we report the molecular, structural, and functional characterization of TCP1δ subunit of <i>Leishmania donovani</i> (LdTCP1δ), the causative agent of Indian kala-azar. LdTCP1δ gene exhibited only 27.9% identity with LdTCP1γ and clustered in a separate branch in the phylogenic tree of LdTCP1 subunits. The purified recombinant protein formed a high molecular weight complex (0.75 MDa), arranged into 16-mer assembly, and performed <i>in vitro</i> chaperonin activity as assayed by ATP-dependent luciferase folding. LdTCP1δ exhibits 1.8-fold upregulated expression in metabolically active, rapidly dividing log phase promastigotes. Over-expression of LdTCP1δ in promastigotes results in increased infectivity and rate of multiplication of intracellular amastigotes. The study thus establishes the existence of an individual functionally active homo-oligomeric complex of LdTCP1δ chaperonin with its role in parasite infectivity and multiplication.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0023424"},"PeriodicalIF":2.9,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11475657/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153922","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":"Heterogeneity of <i>Salmonella enterica</i> lipopolysaccharide counteracts macrophage and antimicrobial peptide defenses.","authors":"Linda M Heffernan, Anna-Lisa E Lawrence, Haley A Marcotte, Amit Sharma, Aria X Jenkins, Damilola Iguwe, Jennifer Rood, Scott W Herke, Mary X O'Riordan, Basel H Abuaita","doi":"10.1128/iai.00251-24","DOIUrl":"10.1128/iai.00251-24","url":null,"abstract":"<p><p>S<i>almonella enterica</i> is comprised of over 2,500 serovars, in which non-typhoidal serovars (NTS), Enteritidis (SE), and Typhimurium (STM) are the most clinically associated with human infections. Although NTS have similar genetic elements to cause disease, phenotypic variation including differences in lipopolysaccharide (LPS) composition may control immune evasion. Here, we demonstrate that macrophage host defenses and LL-37 antimicrobial efficacy against SE and STM are substantially altered by LPS heterogeneity. We found that SE evades macrophage killing by inhibiting phagocytosis while STM survives better intracellularly post-phagocytosis. SE-infected macrophages failed to activate the inflammasomes and subsequently produced less interleukin-1β (IL-1β), IL-18, and interferon λ. Inactivation of LPS biosynthesis genes altered LPS composition, and the SE LPS-altered mutants could no longer inhibit phagocytosis, inflammasome activation, and type II interferon signaling. In addition, SE and STM showed differential susceptibility to the antimicrobials LL-37 and colistin, and alteration of LPS structure substantially increased susceptibility to these molecules. Collectively, our findings highlight that modification of LPS composition by <i>Salmonella</i> increases resistance to host defenses and antibiotics.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0025124"},"PeriodicalIF":2.9,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11475854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119729","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":"RSV enhances <i>Staphylococcus aureus</i> bacterial growth in the lung.","authors":"Helen E Rich, Simran Bhutia, Francina Gonzales de Los Santos, Gabrielle P Entrup, Helen I Warheit-Niemi, Stephen J Gurczynski, Monica Bame, Michael T Douglas, Susan B Morris, Rachel L Zemans, Nicholas W Lukacs, Bethany B Moore","doi":"10.1128/iai.00304-24","DOIUrl":"10.1128/iai.00304-24","url":null,"abstract":"<p><p>Patients coinfected with respiratory syncytial virus (RSV) and bacteria have longer hospital stays, higher risk of intensive care unit admission, and worse outcomes. We describe a model of RSV line 19F/methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) USA300 coinfection that does not impair viral clearance, but prior RSV infection enhances USA300 MRSA bacterial growth in the lung. The increased bacterial burden post-RSV correlates with reduced accumulation of neutrophils and impaired bacterial killing by alveolar macrophages. Surprisingly, reduced neutrophil accumulation is likely not explained by reductions in phagocyte-recruiting chemokines or alterations in proinflammatory cytokine production compared with mice infected with <i>S. aureus</i> alone. Neutrophils from RSV-infected mice retain their ability to migrate toward chemokine signals, and neutrophils from the RSV-infected lung are better able to phagocytize and kill <i>S. aureus ex vivo</i> on a per cell basis. In contrast, while alveolar macrophages could ingest USA300 post-RSV, intracellular bacterial killing was impaired. The RSV/<i>S. aureus</i> coinfected lung promotes a state of overactivation in neutrophils, demonstrated by increased production of reactive oxygen species (ROS) that can drive formation of neutrophil extracellular traps (NETs), resulting in cell death. Mice with RSV/<i>S. aureus</i> coinfection had increased extracellular DNA and protein in bronchoalveolar lavage fluid and histological evidence confirmed NETosis <i>in vivo</i>. Taken together, these data highlight that prior RSV infection can prime the overactivation of neutrophils leading to cell death that impairs neutrophil accumulation in the lung. Additionally, alveolar macrophage killing of bacteria is impaired post-RSV. Together, these defects enhance USA300 MRSA bacterial growth in the lung post-RSV.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0030424"},"PeriodicalIF":2.9,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11475690/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987857","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}