Mucosal Immunology最新文献

{"title":"Intrapulmonary-administered myeloid derived suppressor cells rescue mice from Pseudomonas aeruginosa infection and promote a regulatory/repair phenotype","authors":"Maëlys Born-Bony ,&nbsp;Clémentine Cornu ,&nbsp;Bérengère Villeret ,&nbsp;Valérie Gratio ,&nbsp;Romé Voulhoux ,&nbsp;Jean-Michel Sallenave","doi":"10.1016/j.mucimm.2025.03.001","DOIUrl":"10.1016/j.mucimm.2025.03.001","url":null,"abstract":"<div><div>Pseudomonas aeruginosa (P.aeruginosa) is a pathogenic opportunistic bacterium, classified as a priority by the WHO for the research of new treatments. As this bacterium is harmful through the inflammation and tissue damage it causes, we investigated the role of Myeloid Derived Suppressor Cells (MDSC) in P.aeruginosa infections and their potential as a therapeutic tool. Using both ‘classically’ obtained MDSC (through mice bone-marrow differentiation), and a new procedure developed here (using the ER-Hoxb8 hematopoietic cell line), we observed that after administering intra-nasally a lethal dose of P.aeruginosa (PAO1), intra-pulmonary transfer of MDSC, in both prophylactic and therapeutic protocols, markedly improves survival of <em>P.aeruginosa</em> infected animals. Mechanistically, with a sub-lethal dose of <em>P.aeruginosa</em>, we observed that MDSC transfer modulated lung tissue injury, down-regulated inflammatory responses and elicited lung repair. We further showed that WT-PAO1 and MDSC (and their subtypes PMN-MDSC and M−MDSC) could interact directly <em>in vitro</em> and <em>in vivo</em>, and that both PMN- and M−MDSC gene expression (assessed through RNA sequencing) was modulated after <em>in vitro P.aeruginosa</em> infection, and that WT-PAO1 (but not ΔFlic-PAO1) infection led to inhibition of T cell proliferation and promoted epithelial cell wound healing. Furthermore, we showed that the transcription factor Nr4A1 was up-regulated in both PMN- and M−MDSC- infected cells and may be an important mediator in the process. Altogether, we highlight a potential beneficial role of MDSC in P.aeruginosa infection responses and suggest that the unique properties of these cells make them attractive potential new therapeutic tools for patients with acute or chronic inflammatory diseases.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 3","pages":"Pages 700-716"},"PeriodicalIF":7.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microbial remodeling of gut tryptophan metabolism and indole-3-lactate production regulate epithelial barrier repair and viral suppression in human and simian immunodeficiency virus infections","authors":"Clarissa Santos Rocha ,&nbsp;Katie L. Alexander ,&nbsp;Carolina Herrera ,&nbsp;Mariana G. Weber ,&nbsp;Irina Grishina ,&nbsp;Lauren A. Hirao ,&nbsp;Dylan J. Kramer ,&nbsp;Juan Arredondo ,&nbsp;Abigail Mende ,&nbsp;Katti R. Crakes ,&nbsp;Anne N. Fenton ,&nbsp;Maria L. Marco ,&nbsp;David A. Mills ,&nbsp;John C. Kappes ,&nbsp;Lesley E. Smythies ,&nbsp;Paul Ziprin ,&nbsp;Sumathi Sankaran-Walters ,&nbsp;Phillip D. Smith ,&nbsp;Satya Dandekar","doi":"10.1016/j.mucimm.2025.01.011","DOIUrl":"10.1016/j.mucimm.2025.01.011","url":null,"abstract":"<div><div>Gut inflammatory diseases cause microbial dysbiosis. Human immunodeficiency virus-1 (HIV) infection disrupts intestinal integrity, subverts repair/renewal pathways, impairs mucosal immunity and propels microbial dysbiosis. However, microbial metabolic mechanisms driving repair mechanisms in virally inflamed gut are not well understood. We investigated the capability and mechanisms of gut microbes to restore epithelial barriers and mucosal immunity in virally inflamed gut by using a multipronged approach: an <em>in vivo</em> simian immunodeficiency virus (SIV)-infected nonhuman primate model of HIV/AIDS, <em>ex vivo</em> HIV-exposed human colorectal explants and primary human intestinal epithelial cells. SIV infection reprogrammed tryptophan (TRP) metabolism, increasing kynurenine catabolite levels that are associated with mucosal barrier disruption and immune suppression. Administration of <em>Lactiplantibacillus plantarum</em> or <em>Bifidobacterium longum</em> subsp<em>. infantis</em> into the SIV-inflamed gut lumen <em>in vivo</em> resulted in rapid reprogramming of microbial TRP metabolism towards indole-3-lactic acid (ILA) production. This shift accelerated epithelial repair and enhanced anti-viral defenses through induction of IL-22 signaling in mucosal T cells and aryl hydrocarbon receptor activation. Additionally, ILA treatment of human colorectal tissue explants <em>ex vivo</em> inhibited HIV replication by reducing mucosal inflammatory cytokine production and cell activation. Our findings underscore the therapeutic potential of microbial metabolic reprogramming of TRP-to-ILA and mechanisms in mitigating viral pathogenic effects and bolstering mucosal defenses for HIV eradication.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 3","pages":"Pages 583-595"},"PeriodicalIF":7.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Damage sensing through TLR9 regulates inflammatory and antiviral responses during influenza infection","authors":"Jooyoung Kim ,&nbsp;Yifan Yuan ,&nbsp;Karen Agaronyan ,&nbsp;Amy Zhao ,&nbsp;Victoria D Wang ,&nbsp;David Gau ,&nbsp;Nicholas Toosi ,&nbsp;Gayatri Gupta ,&nbsp;Heran Essayas ,&nbsp;Ayelet Kaminski ,&nbsp;John McGovern ,&nbsp;Sheeline Yu ,&nbsp;Samuel Woo ,&nbsp;Chris J. Lee ,&nbsp;Shifa Gandhi ,&nbsp;Tina Saber ,&nbsp;Tayebeh Saleh ,&nbsp;Buqu Hu ,&nbsp;Ying Sun ,&nbsp;Genta Ishikawa ,&nbsp;Lokesh Sharma","doi":"10.1016/j.mucimm.2025.01.008","DOIUrl":"10.1016/j.mucimm.2025.01.008","url":null,"abstract":"<div><div>Host response aimed at eliminating the infecting pathogen, as well as the pathogen itself, can cause tissue injury. Tissue injury leads to the release of a myriad of cellular components including mitochondrial DNA (mtDNA), which the host senses through pattern recognition receptors. How the sensing of tissue injury by the host shapes the anti-pathogen response remains poorly understood. In this study, we utilized mice that are deficient in toll-like receptor-9 (TLR9), which binds to unmethylated CpG DNA sequences such as those present in bacterial and mtDNA. To avoid direct pathogen sensing by TLR9, we utilized the influenza virus, which lacks ligands for TLR9, to determine how damage sensing by TLR9 contributes to anti-influenza immunity. Our data showed that TLR9-mediated sensing of tissue damage promoted an inflammatory response during early infection, driven by epithelial and myeloid cells. Along with the diminished inflammatory response, the absence of TLR9 led to impaired viral clearance manifested as higher and prolonged influenza components in myeloid cells, including monocytes and macrophages, rendering them highly inflammatory. The persistent inflammation driven by infected myeloid cells led to persistent lung injury and impaired recovery in influenza-infected TLR9-/- mice. Further, we found elevated TLR9 ligands in the plasma samples of patients with influenza infection and its association with the disease severity in hospitalized patients, demonstrating its clinical relevance. Overall, we demonstrated an essential role of damage sensing through TLR9 in promoting anti-influenza immunity and inflammatory response.</div></div><div><h3>Author Summary</h3><div>Tissue damage is an inevitable outcome of clinically relevant lung infections, but the host mechanisms for detecting such damage during infection are not well understood. We investigated the role of Toll-like receptor 9 (TLR9) in sensing tissue damage caused by influenza. Since influenza lacks TLR9 ligands, we hypothesized that TLR9 signaling is driven by tissue damage molecules like mitochondrial DNA (mtDNA). Our data revealed that TLR9 deficiency reduces early inflammatory lung injury but impairs viral clearance, resulting in extensive infection of immune cells, persistent inflammation, and delayed recovery. Myeloid-specific TLR9 deletion ameliorated late-stage inflammatory responses. In humans, influenza-infected individuals exhibited elevated TLR9 activity and mtDNA levels in plasma compared to healthy controls, with higher TLR9 activation potential correlating with severe disease requiring ICU admission. These findings suggest that TLR9-mediated damage sensing triggers both inflammatory tissue injury and viral clearance. These data indicate that TLR9 activity can serve as a crucial biomarker and therapeutic target to limit influenza-induced tissue injury.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 3","pages":"Pages 537-548"},"PeriodicalIF":7.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IL-6 mediates defense against influenza virus by promoting protective antibody responses but not innate inflammation","authors":"F. Piattini,&nbsp;N.D. Sidiropoulos,&nbsp;I. Berest,&nbsp;M. Kopf","doi":"10.1016/j.mucimm.2025.02.001","DOIUrl":"10.1016/j.mucimm.2025.02.001","url":null,"abstract":"<div><div>Influenza virus infection is a leading cause of morbidity and mortality worldwide, posing a significant public health problem. The pro-inflammatory cytokine interleukin-6 (IL-6) has been shown to promote defense against respiratory viral infection, while excessive IL-6 responses have been associated with severe pneumonia. Heterogenous expression of IL-6R and the IL-6-signal transducer subunit (gp130) across many cell types and different signaling modalities have made it difficult to define the precise role of the IL-6/IL-6R pathway <em>in vivo</em>. We generated multiple cell lineage-specific <em>Il6ra</em>-deficient mice and compared them to global <em>Il6ra^-/-</em> and <em>Il-6^-/-</em> mice to dissect the systemic and cell-intrinsic mechanisms for pneumonitis and control of influenza A virus (IAV) infection. Delayed viral clearance and severe morbidity in the global IL-6 knockouts were associated with reduced antibody responses, complement C3 and C5 production, and impaired T follicular helper (Tfh) cell generation. Mice lacking IL-6R exclusively in T cells phenocopied a defect in Tfh cell differentiation and antibody production, although susceptibility to IAV was only mildly affected. Mice lacking IL-6R specifically in B cells mounted normal antibody responses. Moreover, innate pro-inflammatory cytokine responses, myeloid cell infiltration, and adaptive immunity in the lung remained unaffected in <em>Il6ra</em>^fl/fl<em>LysM^Cr</em>^e mice. Our results suggest that IL-6 mediates defense against IAV mainly by generating Tfh cells and promoting local C3 production, which together are required for eliciting protective antibody responses by B cells.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 3","pages":"Pages 596-606"},"PeriodicalIF":7.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell sequencing reveals the same heterogeneity of neutrophils in heatstroke-induced lung and liver injury","authors":"Fuquan Wang ,&nbsp;Yan Zhang ,&nbsp;Miaomiao Sun ,&nbsp;Mengyu Li ,&nbsp;Yu Wang ,&nbsp;Dingyu Zhang ,&nbsp;Shanglong Yao","doi":"10.1016/j.mucimm.2025.03.005","DOIUrl":"10.1016/j.mucimm.2025.03.005","url":null,"abstract":"<div><div>Heatstroke (HS) is typically considered a sepsis-like syndrome caused by hyperthermia, often accompanied by multiple organ dysfunctions (MODS). To explore the mechanisms of MODS, we established a mouse model of HS by exposing mice to a hyperthermic and high-humidity environment. Then, we utilized single-cell RNA sequencing (scRNA-seq) to depict the cellular landscape of HS mice lung tissue and liver tissue. We found that the enhancement of neutrophil infiltration mediated by the “Cxcr2-Cxcl2″ receptor-ligand pair is a prominent feature of HS-induced lung injury. By effectively suppressing the recruitment of neutrophils in HS-induced lung injury, the application of Cxcr2 inhibitor held positive implications for improving HS-induced lung injury. In addition to the chemotactic effect of immune cells on neutrophils, we identified a subcluster of fibroblasts labeled as Col14a1+, which possessed notable chemotactic factor-secretion characteristics and likely exerted a role in the early stages of neutrophil infiltration. Furthermore, our study unveiled significant heterogeneity among neutrophils within the HS-induced lung injury. Particularly, Cd177 + neutrophils exhibited a dominant presence, characterized by heightened pro-inflammatory responses and oxidative stress. In heatstroke-induced liver injury, neutrophils exhibited similar heterogeneous characteristics. Cd177 + neutrophils exhibited an enhanced ability to produce neutrophil extracellular traps (NETs) while lowering the levels of NETs can significantly improve heatstroke-induced lung and liver injury. Additionally, our study identified Cebpe as a key transcriptional regulatory factor in Cd177 + neutrophil differentiation. Knockdown of the expression of Cebpe can suppress the Cd177 + neutrophil differentiation and decrease the expression levels of NETs. Our research indicated a common heterogeneity in neutrophils during MODS in HS. Cd177 + neutrophils contributed to organ damage in HS, and Cebpe may serve as a crucial intervention target in the treatment of HS.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 3","pages":"Pages 742-756"},"PeriodicalIF":7.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sialidase fusion protein protects against influenza infection in a cigarette smoke-induced model of COPD","authors":"Cheng-Yen Chang ,&nbsp;Dominique Armstrong ,&nbsp;John M. Knight ,&nbsp;Trevor V. Gale ,&nbsp;Stephen Hawley ,&nbsp;Max Wang ,&nbsp;Nancy Chang ,&nbsp;David B. Corry ,&nbsp;Farrah Kheradmand","doi":"10.1016/j.mucimm.2025.01.004","DOIUrl":"10.1016/j.mucimm.2025.01.004","url":null,"abstract":"<div><div>First- and secondhand smokers are at an increased risk for influenza virus (IFV)-related respiratory failure and death. Despite approved influenza antiviral treatments, there is an unmet need for treatments that can improve outcomes in populations at risk for respiratory failure, including tobacco users with Chronic Obstructive Pulmonary Disease (COPD). Here we show that the sialidase fusion protein, DAS181, reduced viral burden, mitigated inflammation, and attenuated lung function loss, consistent with broad-spectrum anti-influenza responses in a mouse model of COPD and IFV-A infection. Treatment with DAS181 reprogramed the sialic acid-binding immunoglobulin-like lectins (Siglecs) in alveolar macrophages, increased expression of phagocytic marker CD169, and downregulated inhibitory Siglec-F and Siglec-H molecules. Upon reinfection, mice treated with DAS181 showed activated and protective memory response in the lungs. Collectively, we show that this sialidase fusion protein promotes a beneficial immunomodulatory reaction in the lungs, supporting a new IFV-A therapeutic option for at-risk smokers.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 2","pages":"Pages 467-480"},"PeriodicalIF":7.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"There’s no place like home: How local tissue microenvironments shape the function of innate lymphoid cells","authors":"Luke B. Roberts ,&nbsp;Alanna M. Kelly ,&nbsp;Matthew R. Hepworth","doi":"10.1016/j.mucimm.2025.01.012","DOIUrl":"10.1016/j.mucimm.2025.01.012","url":null,"abstract":"<div><div>Innate lymphoid cells (ILC) have emerged as critical immune effectors with key roles in orchestrating the wider immune response. While ILC are relatively rare cells they are found enriched within discrete microenvironments, predominantly within barrier tissues. An emerging body of evidence implicates complex and multi-layered interactions between cell types, tissue structure and the external environment as key determinants of ILC function within these niches. In this review we will discuss the specific components that constitute ILC-associated microenvironments and consider how they act to determine health and disease. The development of holistic, integrated models of ILC function within complex tissue environments will inform new understanding of the contextual cues and mechanisms that determine the protective versus disease-causing roles of this immune cell family.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 2","pages":"Pages 279-289"},"PeriodicalIF":7.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decidualization-associated recruitment of cytotoxic memory CD8+T cells to the maternal-fetal interface for immune defense","authors":"Xixi Huang ,&nbsp;Tingxuan Yin ,&nbsp;Min Yu ,&nbsp;Guohua Zhu ,&nbsp;Xianyang Hu ,&nbsp;Hailin Yu ,&nbsp;Weijie Zhao ,&nbsp;Jiajia Chen ,&nbsp;Jiangyuan Du ,&nbsp;Qingyu Wu ,&nbsp;Wei Zhang ,&nbsp;Lu Liu ,&nbsp;Meirong Du","doi":"10.1016/j.mucimm.2024.12.007","DOIUrl":"10.1016/j.mucimm.2024.12.007","url":null,"abstract":"<div><div>Decidual CD8⁺T (dCD8⁺T) cells are pivotal in the maintenance of the delicate balance between immune tolerance towards the fetus and immune resistance against pathogens. The endometrium and decidua represent the uterine environments before and during pregnancy, respectively, yet the composition and phenotypic alterations of uterine CD8⁺T cells in these tissues remain unclear. Using flow cytometry and analysis of transcriptome profiles, we demonstrated that human dCD8⁺T and endometrial CD8⁺T (eCD8⁺T) cells exhibited similar T cell differentiation statuses and phenotypes of tissue infiltrating or residency, compared to peripheral CD8⁺T (pCD8⁺T) cells. However, dCD8⁺T cells showed decreased expression of coinhibitory marker (PD-1), chemotaxis marker (CXCR3), and tissue-resident markers (CD69 and CD103), along with increased expression of granzyme B and granulysin, compared to eCD8⁺T cells. In vitro cytotoxicity assays further demonstrated that dCD8⁺T cells had greater effector functions than eCD8⁺T cells. Additionally, both in vitro and in vivo chemotaxis assays confirmed the recruitment of non-resident effector memory T cell subsets to the pregnant decidua, contributing to the dCD8⁺T cell-mediated anti-infection mechanism at the maternal-fetal interface. This work demonstrates dCD8⁺T cells replenished from the circulation retain their cytotoxic capacity, which may serve as an enhanced defense mechanism against infection during pregnancy.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 2","pages":"Pages 366-379"},"PeriodicalIF":7.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"T follicular helper cell expansion and hyperimmunoglobulinemia with spontaneous IgE production to dietary antigens in IgA-deficient mice","authors":"Yasmeen S. El Ansari ,&nbsp;Cynthia Kanagaratham ,&nbsp;Kameryn N. Furiness ,&nbsp;Kailey E. Brodeur ,&nbsp;Pui Y. Lee ,&nbsp;Harald Renz ,&nbsp;Hans C. Oettgen","doi":"10.1016/j.mucimm.2025.01.005","DOIUrl":"10.1016/j.mucimm.2025.01.005","url":null,"abstract":"<div><div>Immunoglobulin A (IgA), the most abundantly produced antibody at mucosal surfaces, is thought to play key roles in immune responses to respiratory and enteric pathogens and in the regulation of commensal colonization. Low IgA levels have been associated with recurrent infections and immune dysregulation, including inflammatory bowel disease and autoimmunity. Levels of IgA in maternal breast milk and infant stool are both inversely associated with the emergence of immune responses to food antigens in infants and, in naturally resolving food sensitivity and immunotherapy protocols, the induction of IgA antibodies to dietary antigens has been associated with the acquisition of food tolerance. Here, we uncover new roles for IgA in intestinal immune homeostasis utilizing IgA Knockout (KO) mice generated by CRISPR/Cas9. IgA-deficient mice exhibit hyperimmunoglobulinemia, with increased levels of IgE and MCPT-1. The hyperimmunoglobulinemia is associated with dysregulated Tfh/Tfr responses in the Peyer’s Patches (PPs) and spontaneous immunoglobulin production to chow diet. These findings shed light on important interactions between IgA, the mucosal immune system, and the regulation of Tfh responses, emphasizing the importance of IgA in maintaining immune homeostasis at mucosal surfaces.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 2","pages":"Pages 481-490"},"PeriodicalIF":7.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NOD1 signaling regulates early tissue inflammation during helminth infection","authors":"Camila de Almeida Lopes ,&nbsp;Thais Leal-Silva ,&nbsp;Flaviane Vieira-Santos ,&nbsp;Jorge Lucas Nascimento Souza ,&nbsp;Chiara Cassia Amorim Oliveira ,&nbsp;Fabricio Marcus Silva Oliveira ,&nbsp;Lucas Kraemer ,&nbsp;Luisa Magalhaes ,&nbsp;Pablo Bara-Garcia ,&nbsp;Byunghyun Kang ,&nbsp;Dario Zamboni ,&nbsp;Remo Castro Russo ,&nbsp;Ricardo Toshio Fujiwara ,&nbsp;Thomas B. Nutman ,&nbsp;Pedro Gazzinelli-Guimaraes ,&nbsp;Lilian Lacerda Bueno","doi":"10.1016/j.mucimm.2024.12.004","DOIUrl":"10.1016/j.mucimm.2024.12.004","url":null,"abstract":"<div><div>The role of innate receptors in initiating the early inflammatory response to helminth larval stages in affected tissues during their life cycle within the host remains poorly understood. Given its pivotal role in detecting microbial elements and eliciting immune responses, exploring the NOD1 receptor could offer crucial insights into immune responses to parasitic infections. By using the larval ascariasis model, the acute model for early <em>Ascaris</em> sp. infection in humans, we report that NOD1 signaling markedly regulates pulmonary tissue inflammation during <em>Ascaris</em> larval migration. Here we show that <em>Ascaris</em>-infected NOD1-deficient mice exhibited a pronounced decrease in macrophage and eosinophil recruitment to the lungs. This diminished cellular recruitment to the lung correlated with impaired production of a mixed cytokine profile including IFN-γ, IL-1β, IL-5, IL-10, IL-17 and IL-33. The attenuated inflammatory response observed in the absence of NOD1 signaling during infection was associated with a notable amelioration in lung dysfunction compared to WT-infected mice. Systemically, NOD1 signaling was also associated with <em>Ascaris</em>-specific IgG2b antibody responses. In summary, our findings highlight a pathogenic role for NOD1 signaling in <em>Ascaris</em>-induced tissue inflammation, underlying hematopoietic cell recruitment and regulating downstream inflammatory cascades associated with the host’s innate immune responses in the tissue triggered by helminth larval migration.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 2","pages":"Pages 339-352"},"PeriodicalIF":7.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}