Mucosal Immunology最新文献_第9页

Dietary protein modulates intestinal dendritic cells to establish mucosal homeostasis 膳食蛋白质调节肠道树突状细胞，建立粘膜稳态。

IF 7.9 2区医学

Mucosal Immunology Pub Date : 2024-10-01 DOI: 10.1016/j.mucimm.2024.06.006

{"title":"Dietary protein modulates intestinal dendritic cells to establish mucosal homeostasis","authors":"","doi":"10.1016/j.mucimm.2024.06.006","DOIUrl":"10.1016/j.mucimm.2024.06.006","url":null,"abstract":"<div><div>Dietary proteins are taken up by intestinal dendritic cells (DCs), cleaved into peptides, loaded to major histocompatibility complexes, and presented to T cells to generate an immune response. Amino acid (AA)-diets do not have the same effects because AAs cannot bind to major histocompatibility complex to activate T cells. Here, we show that impairment in regulatory T cell generation and loss of tolerance in mice fed a diet lacking whole protein is associated with major transcriptional changes in intestinal DCs including downregulation of genes related to DC maturation, activation and decreased gene expression of immune checkpoint molecules. Moreover, the AA-diet had a profound effect on microbiome composition, including an increase in <em>Akkermansia muciniphilia</em> and <em>Oscillibacter</em> and a decrease in <em>Lactococcus lactis</em> and <em>Bifidobacterium</em>. Although microbiome transfer experiments showed that AA-driven microbiome modulates intestinal DC gene expression, most of the unique transcriptional change in DC was linked to the absence of whole protein in the diet. Our findings highlight the importance of dietary proteins for intestinal DC function and mucosal tolerance.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 5","pages":"Pages 911-922"},"PeriodicalIF":7.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141458190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Western diet reduces small intestinal intraepithelial lymphocytes via FXR-Interferon pathway 西式饮食通过 FXR- 干扰素途径减少小肠上皮内淋巴细胞。

IF 7.9 2区医学

Mucosal Immunology Pub Date : 2024-10-01 DOI: 10.1016/j.mucimm.2024.07.001

{"title":"Western diet reduces small intestinal intraepithelial lymphocytes via FXR-Interferon pathway","authors":"","doi":"10.1016/j.mucimm.2024.07.001","DOIUrl":"10.1016/j.mucimm.2024.07.001","url":null,"abstract":"<div><div>The prevalence of obesity in the United States has continued to increase over the past several decades. Understanding how diet-induced obesity modulates mucosal immunity is of clinical relevance. We previously showed that consumption of a high fat, high sugar “Western” diet (WD) reduces the density and function of small intestinal Paneth cells, a small intestinal epithelial cell type with innate immune function. We hypothesized that obesity could also result in repressed gut adaptive immunity. Using small intestinal intraepithelial lymphocytes (IEL) as a readout, we found that in non-inflammatory bowel disease (IBD) subjects, high body mass index correlated with reduced IEL density. We recapitulated this in wild type (WT) mice fed with WD. A 4-week WD consumption was able to reduce IEL but not splenic, blood, or bone marrow lymphocytes, and the effect was reversible after another 2 weeks of standard diet (SD) washout. Importantly, WD-associated IEL reduction was not dependent on the presence of gut microbiota, as WD-fed germ-free mice also showed IEL reduction. We further found that WD-mediated Farnesoid X Receptor (FXR) activation in the gut triggered IEL reduction, and this was partially mediated by intestinal phagocytes. Activated FXR signaling stimulated phagocytes to secrete type I IFN, and inhibition of either FXR or type I IFN signaling within the phagocytes prevented WD-mediated IEL loss. Therefore, WD consumption represses both innate and adaptive immunity in the gut. These findings have significant clinical implications in the understanding of how diet modulates mucosal immunity.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 5","pages":"Pages 1019-1028"},"PeriodicalIF":7.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141590827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Type I IFN signaling in the absence of IRGM1 promotes M. tuberculosis replication in immune cells by suppressing T cell responses 在 IRGM1 缺失的情况下，I 型 IFN 信号通过抑制 T 细胞反应促进结核杆菌在免疫细胞中的复制。

IF 7.9 2区医学

Mucosal Immunology Pub Date : 2024-10-01 DOI: 10.1016/j.mucimm.2024.07.002

Sumanta K. Naik, Michael E. McNehlan, Yassin Mreyoud, Rachel L. Kinsella, Asya Smirnov, Chanchal Sur Chowdhury, Samuel R. McKee, Neha Dubey, Reilly Woodson, Darren Kreamalmeyer, Christina L. Stallings

{"title":"Type I IFN signaling in the absence of IRGM1 promotes M. tuberculosis replication in immune cells by suppressing T cell responses","authors":"Sumanta K. Naik, Michael E. McNehlan, Yassin Mreyoud, Rachel L. Kinsella, Asya Smirnov, Chanchal Sur Chowdhury, Samuel R. McKee, Neha Dubey, Reilly Woodson, Darren Kreamalmeyer, Christina L. Stallings","doi":"10.1016/j.mucimm.2024.07.002","DOIUrl":"10.1016/j.mucimm.2024.07.002","url":null,"abstract":"<div><div>Polymorphisms in the <em>IRGM</em> gene are associated with susceptibility to tuberculosis in humans. A murine ortholog of <em>Irgm</em>, <em>Irgm1</em>, is also essential for controlling <em>Mycobacterium tuberculosis</em> (Mtb) infection in mice. Multiple processes have been associated with IRGM1 activity that could impact the host response to Mtb infection, including roles in autophagy-mediated pathogen clearance and expansion of activated T cells. However, what IRGM1-mediated pathway is necessary to control Mtb infection <em>in vivo</em> and the mechanistic basis for this control remains unknown. We dissected the contribution of IRGM1 to immune control of Mtb pathogenesis <em>in vivo</em> and found that <em>Irgm1</em> deletion leads to higher levels of IRGM3-dependent type I interferon signaling. The increased type I interferon signaling precludes T cell expansion during Mtb infection. The absence of Mtb-specific T cell expansion in <em>Irgm1</em><sup>−/−</sup> mice results in uncontrolled Mtb infection in neutrophils and alveolar macrophages, which directly contributes to susceptibility to infection. Together, our studies reveal that IRGM1 is required to promote T cell-mediated control of Mtb infection in neutrophils, which is essential for the survival of Mtb-infected mice. These studies also uncover new ways type I interferon signaling can impact T<sub>H</sub>1 immune responses.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 5","pages":"Pages 1114-1127"},"PeriodicalIF":7.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141748613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Translocating bacteria in SIV infection are not stochastic and preferentially express cytosine methyltransferases SIV 感染中的转运细菌并非随机，而是优先表达胞嘧啶甲基转移酶。

IF 7.9 2区医学

Mucosal Immunology Pub Date : 2024-10-01 DOI: 10.1016/j.mucimm.2024.07.008

Jacob K. Flynn , Alexandra M. Ortiz , Ivan Vujkovic-Cvijin , Hugh C. Welles , Jennifer Simpson , Fabiola M. Castello Casta , Debra S. Yee , Andrew R. Rahmberg , Kelsie L. Brooks , Marlon De Leon , Samantha Knodel , Kenzie Birse , Laura Noel-Romas , Anshu Deewan , Yasmine Belkaid , Adam Burgener , Jason M. Brenchley

{"title":"Translocating bacteria in SIV infection are not stochastic and preferentially express cytosine methyltransferases","authors":"Jacob K. Flynn , Alexandra M. Ortiz , Ivan Vujkovic-Cvijin , Hugh C. Welles , Jennifer Simpson , Fabiola M. Castello Casta , Debra S. Yee , Andrew R. Rahmberg , Kelsie L. Brooks , Marlon De Leon , Samantha Knodel , Kenzie Birse , Laura Noel-Romas , Anshu Deewan , Yasmine Belkaid , Adam Burgener , Jason M. Brenchley","doi":"10.1016/j.mucimm.2024.07.008","DOIUrl":"10.1016/j.mucimm.2024.07.008","url":null,"abstract":"<div><div>Microbial translocation is a significant contributor to chronic inflammation in people living with HIV (PLWH) and is associated with increased mortality and morbidity in individuals treated for long periods with antiretrovirals. The use of therapeutics to treat microbial translocation has yielded mixed effects, in part, because the species and mechanisms contributing to translocation in HIV remain incompletely characterized. To characterize translocating bacteria, we cultured translocators from chronically SIV-infected rhesus macaques. Proteomic profiling of these bacteria identified cytosine-specific methyltransferases as a common feature and therefore, a potential driver of translocation. Treatment of translocating bacteria with the cytosine methyltransferase inhibitor decitabine significantly impaired growth for several species in vitro. In rhesus macaques, oral treatment with decitabine led to some transient decreases in translocator taxa in the gut microbiome. These data provide mechanistic insight into bacterial translocation in lentiviral infection and explore a novel therapeutic intervention that may improve the prognosis of PLWH.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 5","pages":"Pages 1089-1101"},"PeriodicalIF":7.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141875367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Viral-vectored boosting of OmcB- or CPAF-specific T-cell responses fail to enhance protection from Chlamydia muridarum in infection-immune mice and elicits a non-protective CD8-dominant response in naïve mice 病毒载体增强的 OmcB 或 CPAF 特异性 T 细胞反应不能增强感染免疫小鼠对鼠衣原体的保护能力，并在幼稚小鼠中引起无保护作用的 CD8 优势反应。

IF 7.9 2区医学

Mucosal Immunology Pub Date : 2024-10-01 DOI: 10.1016/j.mucimm.2024.06.012

{"title":"Viral-vectored boosting of OmcB- or CPAF-specific T-cell responses fail to enhance protection from Chlamydia muridarum in infection-immune mice and elicits a non-protective CD8-dominant response in naïve mice","authors":"","doi":"10.1016/j.mucimm.2024.06.012","DOIUrl":"10.1016/j.mucimm.2024.06.012","url":null,"abstract":"<div><div>A vaccine is needed to combat the <em>Chlamydia</em> epidemic. Replication-deficient viral vectors are safe and induce antigen-specific T-cell memory. We tested the ability of intramuscular immunization with modified vaccinia Ankara (MVA) virus or chimpanzee adenovirus (ChAd) expressing chlamydial outer membrane protein (OmcB) or the secreted protein, chlamydial protease-like activating factor (CPAF), to enhance T-cell immunity and protection in mice previously infected with plasmid-deficient <em>Chlamydia muridarum</em> CM972 and elicit protection in naïve mice. MVA.OmcB or MVA.CPAF increased antigen-specific T cells in CM972-immune mice ∼150 and 50-fold, respectively, but failed to improve bacterial clearance. ChAd.OmcB/MVA.OmcB prime-boost immunization of naïve mice elicited a cluster of differentiation (CD) 8-dominant T-cell response dominated by cluster of differentiation (CD)8 T cells that failed to protect. ChAd.CPAF/ChAd.CPAF prime-boost also induced a CD8-dominant response with a marginal reduction in burden. Challenge of ChAd.CPAF-immunized mice genetically deficient in CD4 or CD8 T cells showed that protection was entirely CD4-dependent. CD4-deficient mice had prolonged infection, whereas CD8-deficient mice had higher frequencies of CPAF-specific CD4 T cells, earlier clearance, and reduced burden than wild-type controls. These data reinforce the essential nature of the CD4 T-cell response in protection from chlamydial genital infection in mice and the need for vaccine platforms that drive CD4-dominant responses.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 5","pages":"Pages 1005-1018"},"PeriodicalIF":7.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141538196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Distinct olfactory mucosal macrophage populations mediate neuronal maintenance and pathogen defense 不同的嗅粘膜巨噬细胞群介导神经元维护和病原体防御

IF 7.9 2区医学

Mucosal Immunology Pub Date : 2024-10-01 DOI: 10.1016/j.mucimm.2024.07.009

Sebastian A. Wellford , Ching-Wen Chen , Marko Vukovic , Kristen A. Batich , Elliot Lin , Alex K. Shalek , Jose Ordovas-Montanes , Annie Park Moseman , E. Ashley Moseman

{"title":"Distinct olfactory mucosal macrophage populations mediate neuronal maintenance and pathogen defense","authors":"Sebastian A. Wellford , Ching-Wen Chen , Marko Vukovic , Kristen A. Batich , Elliot Lin , Alex K. Shalek , Jose Ordovas-Montanes , Annie Park Moseman , E. Ashley Moseman","doi":"10.1016/j.mucimm.2024.07.009","DOIUrl":"10.1016/j.mucimm.2024.07.009","url":null,"abstract":"<div><div>The olfactory mucosa is important for both the sense of smell and as a mucosal immune barrier to the upper airway and brain. However, little is known about how the immune system mediates the conflicting goals of neuronal maintenance and inflammation in this tissue. A number of immune cell populations reside within the olfactory mucosa and yet we have little understanding of how these resident olfactory immune cells functionally interact with the chemosensory environment. Identifying these interactions will allow therapeutic manipulations that treat disorders such as post-viral olfactory dysfunction. Macrophages are the most prevalent immune cell type in the uninflamed olfactory mucosa and here, we identify two distinct tissue macrophage populations in murine olfactory mucosa. P2ry12<sup>hi</sup> macrophages are transcriptionally specialized for neuron interactions, closely associated with olfactory neuron cell bodies, long-term tissue residents, and functionally specialized to phagocytose cells and debris, including olfactory neurons. Conversely, MHC Class II<sup>hi</sup> macrophages are transcriptionally dedicated to cytokine production and antigen presentation, localized primarily within the olfactory lamina propria, more rapidly replaced by blood monocytes, and rapidly produce chemokines in response to viral infection. We further show that these macrophage signatures are present in human olfactory biopsies, and P2ry12-like olfactory macrophages are reduced in patients with long-term smell loss following COVID-19. Together, these data show that two olfactory macrophage populations regulate neurons and initiate the immune response, contributing to our understanding of both olfactory immunity and tissue-resident macrophage biology.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 5","pages":"Pages 1102-1113"},"PeriodicalIF":7.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CD38 and extracellular NAD+ regulate the development and maintenance of Hp vaccine‐induced CD4+ TRM in the gastric epithelium CD38 和细胞外 NAD+ 可调节胃上皮细胞中由 Hp 疫苗诱导的 CD4+ TRM 的发育和维持。

IF 7.9 2区医学

Mucosal Immunology Pub Date : 2024-10-01 DOI: 10.1016/j.mucimm.2024.06.011

引用次数: 0

Opposing roles of resident and infiltrating immune cells in the defense against Legionella longbeachae via IL-18R/IFN-γ/ROS axis in mice 常驻和浸润免疫细胞通过 IL-18R/IFN-γ/ROS 轴在小鼠体内防御长须鲸军团菌的过程中发挥相反的作用。

IF 7.9 2区医学

Mucosal Immunology Pub Date : 2024-10-01 DOI: 10.1016/j.mucimm.2024.05.001

{"title":"Opposing roles of resident and infiltrating immune cells in the defense against Legionella longbeachae via IL-18R/IFN-γ/ROS axis in mice","authors":"","doi":"10.1016/j.mucimm.2024.05.001","DOIUrl":"10.1016/j.mucimm.2024.05.001","url":null,"abstract":"<div><div>The immune response against <em>Legionella longbeachae</em>, a causative agent of the often-fatal Legionnaires’ pneumonia, is poorly understood. Here, we investigated the specific roles of tissue-resident alveolar macrophages (AMs) and infiltrating phagocytes during infection with this pathogen. AMs were the predominant cell type that internalized bacteria 1 day after infection. A total of 3 and 5 days after infection, AM numbers were greatly reduced, whereas there was an influx of neutrophils and, later, monocyte-derived cells (MCs) into lung tissue. AMs carried greater numbers of viable <em>L. longbeachae</em> than neutrophils and MCs, which correlated with a higher capacity of <em>L. longbeachae</em> to translocate bacterial effector proteins required for bacterial replication into the AM cytosol. Cell ablation experiments demonstrated that AM promoted infection, whereas neutrophils and MC were required for efficient bacterial clearance. Interleukin (IL)-18 was important for interferon-γ production by IL-18R<sup>+</sup> natural killer cells and T cells, which, in turn, stimulated reactive oxygen species–mediated bactericidal activity in neutrophils, resulting in the restriction of <em>L. longbeachae</em> infection. Ciliated bronchiolar epithelial cells also expressed IL-18R but did not play a role in IL-18–mediated <em>L. longbeachae</em> clearance. Our results have identified opposing innate functions of tissue-resident and infiltrating immune cells during <em>L. longbeachae</em> infection that may be manipulated to improve protective responses.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 5","pages":"Pages 777-792"},"PeriodicalIF":7.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140945495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

IL-23 exerts dominant pathogenic functions in Crohn’s disease-ileitis IL-23在克罗恩病-静脉炎中发挥主导致病功能

IF 7.9 2区医学

Mucosal Immunology Pub Date : 2024-10-01 DOI: 10.1016/j.mucimm.2024.05.008

{"title":"IL-23 exerts dominant pathogenic functions in Crohn’s disease-ileitis","authors":"","doi":"10.1016/j.mucimm.2024.05.008","DOIUrl":"10.1016/j.mucimm.2024.05.008","url":null,"abstract":"<div><div>Crohn’s disease (CD), a main form of Inflammatory Bowel Disease (IBD) is a chronic inflammatory disorder, mainly affecting the ileum. Interleukin (IL)-12 and IL-23 are both targeted by Ustekinumab, a commonly used monoclonal antibody for IBD treatment. However, their specific roles in ileitis have not been extensively explored. Here, we utilized the <em>Tnf</em><sup>ΔΑRE</sup> model of CD-ileitis to probe the functions of IL-12 and IL-23 by employing genetically deficient mice for their respective subunits. Our findings highlight that IL-23, rather than IL-12, plays a pivotal role in the progression of ileitis. IL-23 deficiency resulted in reduced immune cell infiltration in the ileum, and decreased expression of effector cytokines downstream of IL-23 signaling. Interestingly, expanding CD14<sup>+</sup> neutrophils were highly expressing <em>Il23a</em> in the inflamed ileum. Furthermore, the deletion of IL-12 conferred modest additional protection only in the absence of IL-23, suggesting potential compensatory mechanisms between these cytokines. Furthermore, our study suggests that IL-23 may function independently of IL-17, as <em>Il17a</em> deletion exacerbated murine ileitis, consistent with clinical studies in human CD patients using anti–IL-17 inhibitors. This research underscores the significance of targeting IL-23 in CD-ileitis, while the concurrent targeting of both IL-12 and IL-23 should be also considered as an advantageous therapeutic approach.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 5","pages":"Pages 769-776"},"PeriodicalIF":7.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141284212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Extracellular vesicles of Bacteroides uniformis induce M1 macrophage polarization and aggravate gut inflammation during weaning 均匀乳杆菌的胞外囊泡会诱导 M1 巨噬细胞极化，并加剧断奶期间的肠道炎症。

IF 7.9 2区医学

Mucosal Immunology Pub Date : 2024-10-01 DOI: 10.1016/j.mucimm.2024.05.004

{"title":"Extracellular vesicles of Bacteroides uniformis induce M1 macrophage polarization and aggravate gut inflammation during weaning","authors":"","doi":"10.1016/j.mucimm.2024.05.004","DOIUrl":"10.1016/j.mucimm.2024.05.004","url":null,"abstract":"<div><div>Weaning process is commonly associated with gastrointestinal inflammation and dysbiosis of the intestinal microbes. In particular, the impact of gut bacteria and extracellular vesicles on the etiology of intestinal inflammation during weaning is not well understood. We have uncovered a potential link between gut inflammation and the corresponding variation of macrophage bacterial sensing and pro-inflammatory polarization during the weaning process of piglets through single-cell transcriptomic analyses. We conducted a comprehensive analysis of bacterial distribution across the gastrointestinal tract and pinpointed <em>Bacteroides uniformis</em> enriching in piglets undergoing weaning. Next, we found out that exposure to <em>B. uniformis</em>-derived extracellular vesicles (BEVs) exacerbated gut inflammation in a murine colitis model while recruiting and polarizing intestinal macrophages toward a pro-inflammatory phenotype. BEVs modulated the function of macrophages cultured <em>in vitro</em> by suppressing the granulocyte-macrophage colony-stimulating factor/signal transducer and activator of transcription 5/arginase 1 pathway, thereby affecting polarization toward an M1-like state. The effects of BEVs were verified both in the macrophage clearance murine model and by using an adoptive transfer assay. Our findings highlight the involvement of BEVs in facilitating the polarization of pro-inflammatory macrophages and promoting gut inflammation during weaning.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 5","pages":"Pages 793-809"},"PeriodicalIF":7.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141080588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0