{"title":"Macrophage-depleted young mice are beneficial in vivo models to assess the translocation of Klebsiella pneumonia from the gastrointestinal tract to the liver in the elderly","authors":"Hitoshi Tsugawa , Shogo Tsubaki , Rika Tanaka , Sho Nashimoto , Jin Imai , Juntaro Matsuzaki , Katsuto Hozumi","doi":"10.1016/j.micinf.2024.105371","DOIUrl":"10.1016/j.micinf.2024.105371","url":null,"abstract":"<div><div>Pathobionts are commensal intestinal microbiota capable of causing systemic infections under specific conditions, such as environmental changes or aging. However, it is unclear how pathobionts are recognized by the intestinal mucosal immune system under physiological conditions. This study demonstrates that the gut pathobiont <em>Klebsiella pneumoniae</em> causes injury to the epithelium and translocates to the liver in specific pathogen-free mice treated with clodronate-liposomes that depleted macrophages. In the clodronate-liposome-treated mice, indigenous classical <em>K. pneumoniae</em> (cKp) with non-K1/K2 capsular serotypes were isolated from the liver, indicating that gut commensal cKp translocated from the gastrointestinal tract to the liver due to the depletion of intestinal macrophages. Oral inoculation of isolated cKp to clodronate-liposome-treated mice significantly reduced the survival rates compared to that of non-treated mice. Our findings demonstrate that intestinal mucosal macrophages play a pivotal role in sensing commensal cKp and suppressing their translocation to the liver. This study demonstrates that clodronate-liposome-treated mouse models are effective for screening and evaluating drugs that prevent the translocation of cKp to the liver, providing new insights into the development of preventive protocols against <em>K. pneumoniae</em> infection.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 8","pages":"Article 105371"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141288309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Heng Heng , Ling Yang , Zhiwei Zheng , Chen Yang , Xuemei Yang , Wenxing Zhao , Ruanyang Sun , Kaichao Chen , Lianwei Ye , Jun Li , Edward Wai-Chi Chan , Sheng Chen
{"title":"Characterization of Acinetobacter baumannii at a tertiary hospital in Guangzhou: a genomic and clinical study","authors":"Heng Heng , Ling Yang , Zhiwei Zheng , Chen Yang , Xuemei Yang , Wenxing Zhao , Ruanyang Sun , Kaichao Chen , Lianwei Ye , Jun Li , Edward Wai-Chi Chan , Sheng Chen","doi":"10.1016/j.micinf.2024.105380","DOIUrl":"10.1016/j.micinf.2024.105380","url":null,"abstract":"<div><div><span><em>Acinetobacter baumannii</em></span><span><span> (AB) infections have become a global public health<span> concern due to the continued increase in the incidence of infection and the rate of resistance to carbapenems. This study aimed to investigate the genomic features of </span></span>AB<span> strains recovered from a tertiary hospital and assess the clinical implications of the findings. A total of 217 AB strains were collected between 2016 and 2018 at a tertiary hospital in Guangzhou, with 183 (84.33%) being carbapenem-resistant AB (CRAB), with the main mechanism being the carriage of the </span></span><em>bla</em><sub>OXA-23</sub><span> gene. The overall mortality rate<span><span> of patients caused by such strains was 15.21% (n = 33). Artificial lung ventilation and the use of </span>meropenem<span><span> were mortality risk factors in AB-infected patients, while KL2 AB infection was negatively associated. Core genome multilocus sequence typing and clustering analysis were performed on the integrated AB genome collection from the NCBI database and this study to illustrate the population structure among China. The results revealed diverse core genome profiles (n = 17) among AB strains from China, and strains from this single hospital exhibited most of the core genome profiles (n = 13), suggesting genetic variability within the hospital and transmission across the country. These findings show that the high transmission potential of the CRAB strains and </span>meropenem<span> usage that confers a selective advantage of CRAB clinically are two major factors that pose significant challenges to the effective clinical management of AB infections. Understanding the genetic features and transmission patterns of clinical AB strains is crucial for the effective control of infections caused by this pathogen.</span></span></span></span></div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 8","pages":"Article 105380"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141443059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Biomolecular condensates with liquid properties formed during viral infections","authors":"Damien Glon, Benjamin Léonardon, Ariane Guillemot, Aurélie Albertini, Cécile Lagaudrière-Gesbert, Yves Gaudin","doi":"10.1016/j.micinf.2024.105402","DOIUrl":"10.1016/j.micinf.2024.105402","url":null,"abstract":"<div><div>During a viral infection, several membraneless compartments with liquid properties are formed. They can be of viral origin concentrating viral proteins and nucleic acids, and harboring essential stages of the viral cycle, or of cellular origin containing components involved in innate immunity. This is a paradigm shift in our understanding of viral replication and the interaction between viruses and innate cellular immunity.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 8","pages":"Article 105402"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141913284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alexander Swidsinski , Rudolf Amann , Alexander Guschin , Sonja Swidsinski , Vera Loening-Baucke , Werner Mendling , Jack D. Sobel , Ronald F. Lamont , Mario Vaneechoutte , Pedro Vieira Baptista , Catriona S. Bradshaw , Igor Yu Kogan , Аlevtina M. Savicheva , Oleg V. Mitrokhin , Nadezhda W. Swidsinski , Gennadiy T. Sukhikh , Tatjana V. Priputnevich , Inna A. Apolikhina , Yvonne Dörffel
{"title":"Polymicrobial consortia in the pathogenesis of biofilm vaginosis visualized by FISH. Historic review outlining the basic principles of the polymicrobial infection theory","authors":"Alexander Swidsinski , Rudolf Amann , Alexander Guschin , Sonja Swidsinski , Vera Loening-Baucke , Werner Mendling , Jack D. Sobel , Ronald F. Lamont , Mario Vaneechoutte , Pedro Vieira Baptista , Catriona S. Bradshaw , Igor Yu Kogan , Аlevtina M. Savicheva , Oleg V. Mitrokhin , Nadezhda W. Swidsinski , Gennadiy T. Sukhikh , Tatjana V. Priputnevich , Inna A. Apolikhina , Yvonne Dörffel","doi":"10.1016/j.micinf.2024.105403","DOIUrl":"10.1016/j.micinf.2024.105403","url":null,"abstract":"<div><div>The manuscript disputes the exclusive mono-infectious way of thinking, which presumes that for every infection only one pathogen is responsible and sufficient, when infectious vectors, close contact and reduced immunity meet. In situations involving heavily colonized anatomical sites such an approach often ends in insoluble contradictions. Upon critical reflection and evaluation of 20 years research on spatial organization of vaginal microbiota it is apparent, that in some situations, pathogens may act and operate in permanent, structurally organized consortia, whereas its individual components may be innocuous and innocent, failing to express any pathogenic effect. In these cases, consortia are the true pathogens responsible for many infectious conditions, which usually remain unrecognized as long as improperly diagnosed.</div><div>The structure of such consortia can be unraveled using ribosomal fluorescence in situ hybridization (FISH). FISH methodology, that not only offers an ex vivo opportunity to recognize bacterial species, but provides unique physical insight into their specific role in the pathogenesis of polymicrobial infections. Ribosomal FISH technique applied to both, women with bacterial vaginosis (BV) and their male partners, has added significantly to our understanding of the pathogenesis of this condition and contributed to appreciating the mechanisms of polymicrobial, community-based infection, potentially leading to therapeutic advances.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 8","pages":"Article 105403"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141913285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jimena Alvarez Hayes , Bruno Blancá , Juan Pablo Gorgojo, Carlos Baroli, Mariela del Carmen Carrica, Maria Eugenia Rodriguez
{"title":"Bordetella pertussis outer membrane vesicles impair neutrophil bactericidal activity","authors":"Jimena Alvarez Hayes , Bruno Blancá , Juan Pablo Gorgojo, Carlos Baroli, Mariela del Carmen Carrica, Maria Eugenia Rodriguez","doi":"10.1016/j.micinf.2024.105375","DOIUrl":"10.1016/j.micinf.2024.105375","url":null,"abstract":"<div><div><span><span><span>Neutrophils constitute the primary defense against bacterial infections, yet certain pathogens express </span>virulence factors that enable them to subvert neutrophils-mediated killing. Outer </span>membrane vesicles (OMVs) have emerged as a secretory system through which bacteria deliver virulence factors to host cells. OMVs from </span><span><em>Bordetella pertussis</em></span><span>, the etiological agent of whooping cough, are loaded with most of bacterial virulence factors, including CyaA, which plays a key role in </span><em>B. pertussis</em><span> evasion of neutrophils bactericidal activity. In our study, we investigated the role of </span><em>B. pertussis</em> OMVs in bacterial interaction with neutrophils. We observed that interaction of OMVs with neutrophils led to a decrease in the expression of cell surface CR3 and FcγRs, an effect dependent on the CyaA toxin delivered by these vesicles. This decreased receptor expression led to reduced bacterial uptake by neutrophils, irrespective of the presence of opsonic antibodies. Moreover, CyaA delivered by OMVs hindered intracellular bactericidal trafficking, promoting bacterial intracellular survival. When both bacteria and OMVs were opsonized, competition between opsonized OMVs and <em>B. pertussis</em> for FcγRs on neutrophils led to a significant decrease in bacterial uptake. Overall, our findings suggest that <em>B. pertussis</em><span> OMVs promote bacterial survival to the encounter with neutrophils in both naïve and immunized individuals.</span></div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 8","pages":"Article 105375"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141288307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alana B. Byrne , Florencia A. Bonnin , Eduardo L. López , Fernando P. Polack , Laura B. Talarico
{"title":"C1q modulation of antibody-dependent enhancement of dengue virus infection in human myeloid cell lines is dependent on cell type and antibody specificity","authors":"Alana B. Byrne , Florencia A. Bonnin , Eduardo L. López , Fernando P. Polack , Laura B. Talarico","doi":"10.1016/j.micinf.2024.105378","DOIUrl":"10.1016/j.micinf.2024.105378","url":null,"abstract":"<div><div><span><span>Antibody-dependent enhancement (ADE) of dengue virus (DENV) infection is one of the mechanisms contributing to increased severity during heterotypic, secondary infection. The complement protein </span>C1q has been shown to reduce the magnitude of ADE </span><em>in vitro</em>. Therefore, we investigated the mechanisms of C1q modulation of ADE, focusing on processes of viral entry.</div><div><span>Using a model of ADE of DENV-1 infection in human myeloid cell lines<span> in the presence of monoclonal antibodies, 4G2 and 2H2, we found that C1q produced nearly a 40-fold reduction of ADE of DENV-1 in K562 cells, but had no effect in U937 cells. In K562 cells, C1q reduced adsorption of DENV-1/4G2 and exerted a dual inhibitory effect on adsorption and </span></span>internalization of DENV-1/2H2. Distinct endocytic pathways in the presence of antibody corresponded to conditions where C1q produced a differential action. Also, C1q did not affect the intrinsic cell response mediated by FcγR in human myeloid cells.</div><div><span>The modulation of ADE of DENV-1 by C1q is dependent on the FcγR expressed on immune cells and the specificity of the antibody comprising the immune complex. Understanding protective and pathogenic mechanisms in the </span>humoral response to DENV infections is crucial for the successful design of antivirals and vaccines.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 8","pages":"Article 105378"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141331400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Muhammad Iqhrammullah , Rika Yusnaini , Shakira Amirah , Intan Chaharunia Mulya , Ghina Tsurayya , Muhammad Alif Naufal , Sukmawan Fajar Santosa , Harapan Harapan , Baidillah Zulkifli
{"title":"Effect of tuberculosis-specific antigen stimulation on the diagnostic accuracy of interferon-γ inducible protein-10 in distinguishing active and latent tuberculosis infection: a meta-analysis","authors":"Muhammad Iqhrammullah , Rika Yusnaini , Shakira Amirah , Intan Chaharunia Mulya , Ghina Tsurayya , Muhammad Alif Naufal , Sukmawan Fajar Santosa , Harapan Harapan , Baidillah Zulkifli","doi":"10.1016/j.micinf.2024.105396","DOIUrl":"10.1016/j.micinf.2024.105396","url":null,"abstract":"<div><h3>Background</h3><div>Identifying active tuberculosis (ATB) from latent tuberculosis infection (LTBI) persists as a challenge, and interferon-γ inducible protein-10 (IP-10) has been employed as the solution. To further improve its diagnostic performance, the sample can be stimulated with TB specific antigen (TBAg).</div></div><div><h3>Aim</h3><div>To perform meta-analysis on diagnostic accuracy of unstimulated and TBAg-stimulated IP-10 in differentiating ATB from LTBI.</div></div><div><h3>Methods</h3><div>Systematic search was performed on five major scientific databases as of 29 November 2023. Observational studies reporting diagnostic values of unstimulated or TBAg-stimulated IP-10 in identifying ATB from LTBI were included. Meta-analysis was carried out using two-level mixed-effect logistic regression model.</div></div><div><h3>Results</h3><div>Twenty-five studies recruiting 2301 patients (1137 ATB versus 1164 LTBI) were included in the quantitative analysis. The pooled sensitivity and specifity of IP-10 were 72% (95%CI: 0.59–0.82) and 78% (95%CI: 0.63–0.88), respectively. As for TBAg-stimulated IP-10, the sensitivity and specifity were 82% (95%CI: 0.76–0.87) and 85% (95%CI: 0.73–0.92), respectively. The senstivity was reduced signiticantly (<em>p</em> < 0.01) when the patients with human immunodeficiency virus infection were included, except after the TBAg stimulation.</div></div><div><h3>Conclusion</h3><div>Stimulating IP-10 with TBAg could improve the diagnostic accuracy in differentiating ATB from LTBI.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 8","pages":"Article 105396"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141734625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Qi Wang , Xiaomeng Tang , Wenying Qiao , Lina Sun , Han Shi , Dexi Chen , Bin Xu , Yanmin Liu , Juan Zhao , Chunyang Huang , Ronghua Jin
{"title":"Machine learning-based characterization of the gut microbiome associated with the progression of primary biliary cholangitis to cirrhosis","authors":"Qi Wang , Xiaomeng Tang , Wenying Qiao , Lina Sun , Han Shi , Dexi Chen , Bin Xu , Yanmin Liu , Juan Zhao , Chunyang Huang , Ronghua Jin","doi":"10.1016/j.micinf.2024.105368","DOIUrl":"10.1016/j.micinf.2024.105368","url":null,"abstract":"<div><h3>Background</h3><div><span>Primary biliary cholangitis (PBC) is associated closely with the </span>gut microbiota<span><span>. This study aimed to explore the characteristics of the gut microbiota after the progress of PBC to </span>cirrhosis.</span></div></div><div><h3>Method</h3><div>This study focuses on utilizing the 16S rRNA<span> gene sequencing method to screen for differences in gut microbiota<span> in PBC patients who progress to cirrhosis. Then, we divided the data into training and verification sets and used seven different machine learning (ML) models to validate them respectively, calculating and comparing the accuracy, F1 score, precision, and recall, and screening the dominant intestinal flora affecting PBC cirrhosis.</span></span></div></div><div><h3>Result</h3><div><span>PBC cirrhosis patients showed decreased diversity and richness of gut microbiota. Additionally, there are alterations in the composition of gut microbiota in PBC cirrhosis patients. The abundance of </span><span><span>Faecalibacterium</span></span> and <em>Gemmiger</em> bacteria significantly decreases, while the abundance of <span><span>Veillonella</span></span> and <span><span>Streptococcus</span></span> significantly increases. Furthermore, machine learning methods identify <span><span>Streptococcus</span></span> and <em>Gemmiger</em> as the predominant gut microbiota in PBC patients with cirrhosis, serving as non-invasive biomarkers (AUC = 0.902).</div></div><div><h3>Conclusion</h3><div>Our study revealed that PBC cirrhosis patients gut microbiota composition and function have significantly changed. <em>Streptococcus</em> and <em>Gemmiger</em> may become a non-invasive biomarker for predicting the progression of PBC progress to cirrhosis.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 8","pages":"Article 105368"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141137069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ming Lei , Yanheng Tan , Jingyi Ke , Mengqi Wang , Zeyang He , Guangshuo Ou , Haijun Tu , Weihong Tan
{"title":"Loss of cilia in chemosensory neurons inhibits pathogen avoidance in Caenorhabditis elegans","authors":"Ming Lei , Yanheng Tan , Jingyi Ke , Mengqi Wang , Zeyang He , Guangshuo Ou , Haijun Tu , Weihong Tan","doi":"10.1016/j.micinf.2024.105370","DOIUrl":"10.1016/j.micinf.2024.105370","url":null,"abstract":"<div><div>Pathogen avoidance is a crucial and evolutionarily conserved behavior that enhances survival by preventing infection in diverse species, including <span><span>Caenorhabditis elegans</span></span> (<em>C. elegans</em>). This behavior relies on multiple chemosensory neurons equipped with cilia that are exposed to the external environment. However, the specific role of neuronal cilia in pathogen avoidance has not been completely elucidated. Herein, we discovered that <em>osm-3(p802)</em> mutants, which lack chemosensory neuronal cilia, exhibit slower avoidance of the pathogen <span><span>Pseudomonas aeruginosa</span></span><span> PA14, but not </span><em>Escherichia coli</em> OP50. This observation was consistent when <em>osm-3(p802)</em> mutants were exposed to <em>P. aeruginosa</em><span> PAO1. Following an encounter with PA14, the pumping, thrashing, and defecation behaviors of </span><em>osm-3</em> mutants were comparable to those of the wild-type. However, the <em>osm-3</em><span> mutants demonstrated reduced intestinal colonization of PA14, suggesting that they have stronger intestinal clearance ability. We conducted RNA-seq to identify genes responding to external stimuli that were differentially expressed owing to the loss of </span><em>osm-3</em><span> and PA14 infection. Using RNAi, we demonstrated that three of these genes were essential for normal pathogen avoidance. In conclusion, our findings demonstrate that the loss of chemosensory neuronal cilia reduces pathogen avoidance in </span><em>C. elegans</em> while delaying intestinal colonization.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 8","pages":"Article 105370"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141284109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Thomas Belcher , Loïc Coutte , Anne-Sophie Debrie, Valentin Sencio, François Trottein, Camille Locht , Stephane Cauchi
{"title":"Pertussis toxin-dependent and -independent protection by Bordetella pertussis against influenza","authors":"Thomas Belcher , Loïc Coutte , Anne-Sophie Debrie, Valentin Sencio, François Trottein, Camille Locht , Stephane Cauchi","doi":"10.1016/j.micinf.2024.105404","DOIUrl":"10.1016/j.micinf.2024.105404","url":null,"abstract":"<div><div>Bacterial-viral co-infections are frequent, but their reciprocal effects are not well understood. Here, we examined the effect <em>Bordetella pertussis</em> infection and the role of pertussis toxin (PT) on influenza A virus (IAV) infection and disease. In C57BL/6J mice, prior nasal administration of virulent <em>B. pertussis</em> BPSM and PT-deficient BPRA provided effective and sustained protection from IAV-induced mortality. However, BPSM or BPRA administered together with purified PT (BPRA + PT) had a stronger protective effect on weight loss compared to BPRA alone, reduced the viral load, and induced IL-17A in the lungs. In IL-17<sup>−/−</sup> mice, BPSM- and BPRA + PT-mediated protection against viral replication was abolished, while BPSM, BPRA and BPRA + PT provided similar levels of protection against IAV-induced mortality and weight loss. In conclusion, <em>B. pertussis</em> infection protects against influenza by two mechanisms: one reducing viral replication depending on PT and IL-17, and the other, independently of PT and IL-17, resulting in protection against influenza disease without reducing the viral load.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 8","pages":"Article 105404"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141917087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}