Mucosal Immunology最新文献_第5页

Inducible, but not constitutive, pancreatic REG/Reg isoforms are regulated by intestinal microbiota and pancreatic diseases 诱导型而非构成型胰腺REG/ REG异构体受肠道微生物群和胰腺疾病的调节。

IF 7.6 2区医学

Mucosal Immunology Pub Date : 2025-08-01 DOI: 10.1016/j.mucimm.2025.05.003

Yixuan D. Zhou , Macy R. Komnick , Fabiola Sepulveda , Grace Liu , Elida Nieves-Ortiz , Kelsey Meador , Ornella Ndatabaye , Aliia Fatkhullina , Asha Bozicevich , Braden Juengel , Natalie J. Wu-Woods , Paulina M. Naydenkov , Johnathan Kent , Nathaniel Christiansen , Maria Lucia Madariaga , Piotr Witkowski , Rustem F. Ismagilov , Daria Esterházy

{"title":"Inducible, but not constitutive, pancreatic REG/Reg isoforms are regulated by intestinal microbiota and pancreatic diseases","authors":"Yixuan D. Zhou , Macy R. Komnick , Fabiola Sepulveda , Grace Liu , Elida Nieves-Ortiz , Kelsey Meador , Ornella Ndatabaye , Aliia Fatkhullina , Asha Bozicevich , Braden Juengel , Natalie J. Wu-Woods , Paulina M. Naydenkov , Johnathan Kent , Nathaniel Christiansen , Maria Lucia Madariaga , Piotr Witkowski , Rustem F. Ismagilov , Daria Esterházy","doi":"10.1016/j.mucimm.2025.05.003","DOIUrl":"10.1016/j.mucimm.2025.05.003","url":null,"abstract":"<div><div>The <em>REG</em>/<em>Reg</em> gene locus encodes a conserved family of potent antimicrobial but also pancreatitis-associated proteins. Here we investigated whether <em>REG/Reg</em> family members differ in their baseline expression levels and abilities to be regulated in the pancreas and gut upon perturbations. We found, in humans and mice, the pancreas and gut differed in <em>REG</em>/<em>Reg</em> isoform levels and preferences, with the duodenum most resembling the pancreas. Pancreatic acinar cells and intestinal enterocytes were the dominant REG producers. Intestinal symbiotic microbes regulated the expression of the same, select <em>Reg</em> members in gut and pancreas. These <em>Reg</em> members had the most STAT3-binding sites close to the transcription start sites and were partially IL-22 dependent. We thus categorized them as “inducible” and others as “constitutive”. Indeed, in pancreatic ductal adenocarcinoma and pancreatitis models, only inducible <em>Reg</em> members were upregulated in the pancreas. While intestinal <em>Reg</em> expression remained unchanged upon pancreatic perturbation, pancreatitis altered the microbial composition of the duodenum and feces shortly after disease onset. Our study reveals differential usage and regulation of <em>REG</em>/<em>Reg</em> isoforms as a mechanism for tissue-specific innate immunity, highlights the intimate connection of pancreas and duodenum, and implies a gut-to-pancreas communication axis resulting in a coordinated <em>Reg</em> response.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 4","pages":"Pages 918-936"},"PeriodicalIF":7.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120342","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}

引用次数: 0

Living on the edge: Mucus-associated microbes in the colon 生活在边缘：结肠中与黏液相关的微生物。

IF 7.6 2区医学

Mucosal Immunology Pub Date : 2025-08-01 DOI: 10.1016/j.mucimm.2025.04.003

Mihovil Joja , Erica T. Grant , Mahesh S. Desai

引用次数: 0

Corrigendum to “Distinct cell death pathways induced by granzymes collectively protect against intestinal Salmonella infection” [Mucosal. Immun. 17 (2024) 1242–1255] “颗粒酶诱导的不同细胞死亡途径共同保护肠道沙门氏菌感染”[粘膜]的更正。免疫学。17 (2024)1242-1255]

IF 7.6 2区医学

Mucosal Immunology Pub Date : 2025-08-01 DOI: 10.1016/j.mucimm.2025.06.003

Amanpreet Singh Chawla , Maud Vandereyken , Maykel Arias , Llipsy Santiago , Dina Dikovskaya , Chi Nguyen , Neema Skariah , Nicolas Wenner , Natasha B. Golovchenko , Sarah J. Thomson , Edna Ondari , Marcela Garzón-Tituaña , Christopher J. Anderson , Megan Bergkessel , Jay C.D. Hinton , Karen L. Edelblum , Julian Pardo , Mahima Swamy

引用次数: 0

Gut microbiota regulates intestinal goblet cell response and mucin production by influencing the TLR2-SPDEF axis in an enteric parasitic infection 肠道微生物群通过影响肠道寄生虫感染中的TLR2-SPDEF轴调节肠杯状细胞反应和粘蛋白产生。

IF 7.6 2区医学

Mucosal Immunology Pub Date : 2025-08-01 DOI: 10.1016/j.mucimm.2025.03.007

Yeganeh Yousefi , Zarin Haider , Jensine A. Grondin , Huaqing Wang , Sabah Haq , Suhrid Banskota , Tyler Seto , Michael Surette , Waliul I. Khan

{"title":"Gut microbiota regulates intestinal goblet cell response and mucin production by influencing the TLR2-SPDEF axis in an enteric parasitic infection","authors":"Yeganeh Yousefi , Zarin Haider , Jensine A. Grondin , Huaqing Wang , Sabah Haq , Suhrid Banskota , Tyler Seto , Michael Surette , Waliul I. Khan","doi":"10.1016/j.mucimm.2025.03.007","DOIUrl":"10.1016/j.mucimm.2025.03.007","url":null,"abstract":"<div><div>Alterations in goblet cell biology constitute one of the most effective host responses against enteric parasites. In the gastrointestinal (GI) tract, millions of bacteria influence these goblet cell responses by binding to pattern recognition receptors such as toll-like receptors (TLRs). Studies suggest that the gut microbiota also interacts bidirectionally with enteric parasites, including <em>Trichuris muris</em>. Here, we study the roles of <em>T. muris</em>-altered microbiota and the TLR2-SPDEF axis in parasitic host defense. In acute <em>T. muris</em> infection, we observed altered gut microbiota composition, which, when transferred to germ-free mice, resulted in increased goblet cell numbers, Th2 cytokines and <em>Muc2</em> expression, as well as increased <em>Tlr2</em>. Further, antibiotic (ABX)-treated TLR2<sup>-/-</sup> mice, despite having received the same <em>T. muris</em>-altered microbiota, displayed diminished Th2 response, <em>Muc2</em> expression, and, intriguingly, diminished SPDEF expression compared to wildtype counterparts. When infected with <em>T. muris</em>, <em>SPDEF<sup>-/-</sup></em> mice exhibited a reduced Th2 response and altered microbial composition compared to <em>SPDEF<sup>+/+</sup></em>, particularly on day 14 post-infection, and this microbiota was sufficient to alter host goblet cell response when transferred to ABX-treated mice. Taken together, our findings suggest the TLR2-SPDEF axis, via <em>T. muris</em>-induced microbial changes, is an important regulator of goblet cell function and host’s parasitic defense.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 4","pages":"Pages 810-824"},"PeriodicalIF":7.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753442","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}

引用次数: 0

Hypertonic intranasal vaccines gain nasal epithelia access to exert strong immunogenicity 高渗鼻内疫苗可进入鼻腔上皮细胞，发挥强大的免疫原性。

IF 7.6 2区医学

Mucosal Immunology Pub Date : 2025-08-01 DOI: 10.1016/j.mucimm.2025.03.006

Soichiro Hashimoto , Toshiro Hirai , Koki Ueda , Mako Kakihara , Nagisa Tokunoh , Chikako Ono , Yoshiharu Matsuura , Kazuo Takayama , Yasuo Yoshioka

{"title":"Hypertonic intranasal vaccines gain nasal epithelia access to exert strong immunogenicity","authors":"Soichiro Hashimoto , Toshiro Hirai , Koki Ueda , Mako Kakihara , Nagisa Tokunoh , Chikako Ono , Yoshiharu Matsuura , Kazuo Takayama , Yasuo Yoshioka","doi":"10.1016/j.mucimm.2025.03.006","DOIUrl":"10.1016/j.mucimm.2025.03.006","url":null,"abstract":"<div><div>Intranasal vaccines potentially offer superior protection against viral infections compared with injectable vaccines. The immunogenicity of intranasal vaccines including adenovirus vector (AdV), has room for improvement, while few options are available for safe execution. In this study, we demonstrate that modifying a basic parameter of vaccine formulation, i.e., osmolarity, can significantly enhance the immunogenicity of intranasal vaccines. Addition of glycerol to AdV intranasal vaccine solutions, unlike other viscous additives, enhanced systemic and mucosal antibodies as well as resident memory T cells in the nasal tissues, which could protect nasal tissue and the lungs against influenza virus. While viscous glycerol could not prolong intranasal retention of solutes, it promoted AdV infection of nasal epithelial cells by facilitating AdV access to the nasal epithelial cell. The enhanced immunogenicity was induced by the hypertonicity of vaccine preparations and sodium chloride, glucose, and mannitol demonstrated the capacity to enhance immunogenicity. Moreover, hypertonic glycerol enhanced the immunogenicity of adjuvanted subunit intranasal vaccines, but not subunit vaccines without adjuvant or injectable vaccines. Overall, the delivery of intranasal vaccines to nasal epithelial cells could be improved through a simple approach, potentially resulting in stronger immunogenicity for certain vaccines.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 4","pages":"Pages 793-809"},"PeriodicalIF":7.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780563","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}

引用次数: 0

Anti-ST2 antibody reduces airway hyperresponsiveness mediated by monocyte-derived macrophages during influenza A infection 抗st2抗体降低甲型流感感染期间由单核细胞来源的巨噬细胞介导的气道高反应性。

IF 7.6 2区医学

Mucosal Immunology Pub Date : 2025-08-01 DOI: 10.1016/j.mucimm.2025.04.008

Rohin Chakraborty, Julia Chronopoulos, Rui Sun, Arina Morozan, Sydney Joy, Maziar Divangahi, Anne-Marie Lauzon, James G. Martin

{"title":"Anti-ST2 antibody reduces airway hyperresponsiveness mediated by monocyte-derived macrophages during influenza A infection","authors":"Rohin Chakraborty, Julia Chronopoulos, Rui Sun, Arina Morozan, Sydney Joy, Maziar Divangahi, Anne-Marie Lauzon, James G. Martin","doi":"10.1016/j.mucimm.2025.04.008","DOIUrl":"10.1016/j.mucimm.2025.04.008","url":null,"abstract":"<div><div>Influenza A virus (IAV) infections trigger asthma attacks and cause airway hyperresponsiveness (AHR) in murine models. However, the mechanism by which AHR is induced remains to be fully elucidated. Here, we show that targeting the interleukin (IL)–33 suppression of tumorigenicity 2 (ST2) receptor complex with an anti-ST2 antibody during acute IAV infection of C57BL/6 mice reduced AHR, without affecting expansion of ILC2s and independently of IL-13. Among the lung inflammatory cells, the anti-ST2 antibody selectively reduced the monocyte-derived macrophages (MMs). Furthermore, AHR was reduced in C–C chemokine receptor 2 (CCR2)-knockout mice that have deficient MM recruitment. Depletion of MMs achieved by anti-Ly6C antibody administration also reduced AHR. The treatment of airway smooth muscle (ASM) with conditioned medium from IL-33-treated human THP-1-derived macrophages enhanced potassium chloride-induced ASM contraction. These findings suggest that MMs contribute to acute AHR following IAV infection in an IL-33-dependent manner, but independent of the ILC2/IL-13 axis. Additionally, IL-33 stimulates the release of macrophage-derived mediators that enhance airway smooth muscle contraction, offering a potential mechanistic basis for IAV-induced AHR.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 4","pages":"Pages 887-898"},"PeriodicalIF":7.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144012090","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}

引用次数: 0

A multi-omics microbiome signature is associated with the benefits of gastric bypass surgery and is differentiated from diet induced weight loss through 2 years of follow-up 多组学微生物组特征与胃旁路手术的益处相关，并通过2 年的随访与饮食引起的体重减轻区分开来。

IF 7.6 2区医学

Mucosal Immunology Pub Date : 2025-08-01 DOI: 10.1016/j.mucimm.2025.04.002

Vancheswaran Gopalakrishnan , Chanchal Kumar , Ida Robertsen , Christopher Morehouse , Ben Sparklin , Shameer Khader , Ian Henry , Line Kristin Johnson , Jens K. Hertel , Hege Christensen , Rune Sandbu , Peter J. Greasley , Bret R. Sellman , Anders Åsberg , Shalini Andersson , Rasmus Jansson Löfmark , Jøran Hjelmesæth , Cecilia Karlsson , Taylor S. Cohen

{"title":"A multi-omics microbiome signature is associated with the benefits of gastric bypass surgery and is differentiated from diet induced weight loss through 2 years of follow-up","authors":"Vancheswaran Gopalakrishnan , Chanchal Kumar , Ida Robertsen , Christopher Morehouse , Ben Sparklin , Shameer Khader , Ian Henry , Line Kristin Johnson , Jens K. Hertel , Hege Christensen , Rune Sandbu , Peter J. Greasley , Bret R. Sellman , Anders Åsberg , Shalini Andersson , Rasmus Jansson Löfmark , Jøran Hjelmesæth , Cecilia Karlsson , Taylor S. Cohen","doi":"10.1016/j.mucimm.2025.04.002","DOIUrl":"10.1016/j.mucimm.2025.04.002","url":null,"abstract":"<div><div>Roux-en-Y gastric bypass (GBP) surgery is an effective treatment for reducing body weight and correcting metabolic dysfunction in individuals with severe obesity. Herein, we characterize the differences between very low energy diet (VLED) and GBP induced weight loss by multi-omic analyses of microbiome and host features in a non-randomized, controlled, single-center study. Eighty-eight participants with severe obesity were recruited into two arms – GBP versus VLED with matching weight loss for 6 weeks and 2-years of follow-up. A dramatic shift in the distribution of gut microbial taxa and their functional capacity was seen in the GBP group at Week 2 after surgery and was sustained through 2 years. Multi-omic analyses were performed after 6 weeks of matching weight loss between the GBP and VLED groups, which pointed to microbiome derived metabolites such as indoxyl sulphate as characterizing the GBP group. We also identified an inverse association between <em>Streptococcus parasanguinis</em> (an oral commensal) and plasma levels of tryptophan and tyrosine. These data have important implications, as they reveal a significant robust restructuring of the microbiome away from a baseline dysbiotic state in the GBP group. Furthermore, multi-omics modelling points to potentially novel mechanistic insights at the intersection of the microbiome and host.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 4","pages":"Pages 825-835"},"PeriodicalIF":7.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143993830","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}

引用次数: 0

Diet-induced dyslipidemia enhances IFN-γ production in mycolic acid-specific T cells and affects mycobacterial control 饮食诱导的血脂异常增强了霉菌酸特异性T细胞中IFN-γ的产生并影响分枝杆菌的控制。

IF 7.6 2区医学

Mucosal Immunology Pub Date : 2025-08-01 DOI: 10.1016/j.mucimm.2025.04.009

Yen-Lin Lin, Chyung-Ru Wang

{"title":"Diet-induced dyslipidemia enhances IFN-γ production in mycolic acid-specific T cells and affects mycobacterial control","authors":"Yen-Lin Lin, Chyung-Ru Wang","doi":"10.1016/j.mucimm.2025.04.009","DOIUrl":"10.1016/j.mucimm.2025.04.009","url":null,"abstract":"<div><div>Dyslipidemia, characterized by altered lipid profiles, influences host immune responses against infections, including <em>Mycobacterium tuberculosis</em> (Mtb). While the effects of dyslipidemia on conventional T cell responses are well documented, its impact on group 1-CD1 restricted T cells, a distinct subset of lipid antigen-specific unconventional T cells, during Mtb infection remains unclear. In this study, we developed a double-transgenic mouse model expressing human group 1 CD1 (hCD1Tg) and mycolic acid (MA)-specific CD1b-restricted T cell receptor (DN1Tg) in a Rag-deficient and low-density lipoprotein receptor-deficient background to investigate how diet-induced dyslipidemia affects the functionality of MA-specific T cells and their role in anti-Mtb immunity. We found that diet-induced dyslipidemia led to increased IFN-γ production by MA-specific T cells, which promoted mycobacterial clearance <em>in vitro</em>. Mechanistically, this enhanced IFN-γ production was associated with increased TCR signaling and enhanced glycolysis in DN1 T cells, rather than changes in antigen presentation by dendritic cells. However, dyslipidemia also increased apoptosis in DN1 T cells, which may have impaired their ability to control mycobacterial infection <em>in vivo</em>, resulting in reduced bacterial clearance. These findings highlight a complex interplay between diet-induced dyslipidemia and lipid antigen-specific T-cell responses in Mtb infection, providing insights for potential therapeutic strategies to mitigate dyslipidemia-induced changes in T-cell functions.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 4","pages":"Pages 899-910"},"PeriodicalIF":7.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144003450","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}

引用次数: 0

Notch-activated basophils support intestinal CD4+ T cell fate and function during Trichuris muris infection 缺口激活的嗜碱性粒细胞支持寄生虫感染期间肠道CD4+ T细胞的命运和功能。

IF 7.6 2区医学

Mucosal Immunology Pub Date : 2025-08-01 DOI: 10.1016/j.mucimm.2025.05.004

Lauren M. Webb , Lindsey M. Warner , Eric Y. Helm, Bridget M. Mooney, Pavithra Sundaravaradan, Macy K. Matheson, Tighe Christopher, Alejandra Lopez Espinoza, Elia D. Tait Wojno

{"title":"Notch-activated basophils support intestinal CD4+ T cell fate and function during Trichuris muris infection","authors":"Lauren M. Webb , Lindsey M. Warner , Eric Y. Helm, Bridget M. Mooney, Pavithra Sundaravaradan, Macy K. Matheson, Tighe Christopher, Alejandra Lopez Espinoza, Elia D. Tait Wojno","doi":"10.1016/j.mucimm.2025.05.004","DOIUrl":"10.1016/j.mucimm.2025.05.004","url":null,"abstract":"<div><div>Helminth infections affect billions of people worldwide and cause substantial morbidity. Intestinal helminth infection provokes Type 2 inflammation orchestrated by CD4<sup>+</sup> T helper type 2 (Th2) cells. Th2 cells cooperate with group 2 innate lymphoid cells (ILC2s) to produce interleukin (IL)-4 and IL-13 that prompt an epithelial “weep and sweep” response to drive parasite clearance. Tissue-specific cues optimize CD4<sup>+</sup> T cell responses, but the mechanisms regulating intestinal Th2 responses remain unclear. Previously, we identified that the Notch signaling pathway in basophils, rare granulocytes, drove effective parasite clearance and an optimal Th2 response during <em>Trichuris muris</em> infection, a mouse model of human whipworm infection. Here we report that basophil-intrinsic Notch was required for infection-elicited Th2 cytokine responses and a broader IL-4 production program across intestinal CD4<sup>+</sup> T cell subsets. <em>In vitro</em>, basophils supported CD4<sup>+</sup> T cell IL-4 production in a contact-dependent manner, independent of basophil-secreted factors and MHC class II, but dependent on autocrine IL-4 production from CD4<sup>+</sup> T cells. <em>In vivo</em>, basophil-intrinsic Notch mediated basophil-Th2 cell interactions in the cecum during infection. Thus, Notch-programmed basophils act in a contact-dependent manner to optimize intestinal CD4<sup>+</sup> T cell function during helminth infection. These findings improve our understanding of the tissue-specific mechanisms regulating intestinal CD4<sup>+</sup> T cell responses at inflamed mucosal barriers during Type 2 immunity.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 4","pages":"Pages 937-950"},"PeriodicalIF":7.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094462","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}

引用次数: 0

Parasite and host immune factors that impact the development of a mucosal vaccine for Cryptosporidium 影响隐孢子虫粘膜疫苗研制的寄生虫和宿主免疫因素。

IF 7.6 2区医学

Mucosal Immunology Pub Date : 2025-08-01 DOI: 10.1016/j.mucimm.2025.05.002

Maria Merolle, Boris Striepen, Christopher A. Hunter

引用次数: 0