title: Peritoneal cavity is a route for gut-derived microbial signals to promote autoimmunity in non-obese diabetic mice.
abstract: Macrophages play a crucial role in innate immune reactions, and peritoneal macrophages (PMs) guard the sterility of this compartment mainly against microbial threat from the gut. Type 1 diabetes (T1D) is an autoimmune disease in which gut microbiota and gut immune system appear to contribute to disease pathogenesis. We have recently reported elevated free radical production and increased permeability of gut epithelium in non-obese diabetic (NOD) mice. Impaired barrier function could lead to bacterial leakage to the peritoneal cavity. To explore the consequences of impaired gut barrier function on extra-intestinal immune regulation, we characterized peritoneal lavage cells from young newly weaned NOD mice. We detected a rapid increase in the number of macrophages 1-2 weeks after weaning in NOD mice compared to C57BL/6 and BALB/c mice. Interestingly, this increase in macrophages was abrogated in NOD mice that were fed an antidiabetogenic diet (ProSobee), which improves gut barrier function. Macrophages in young (5-week-old) NOD mice displayed a poor TNF-α cytokine response to LPS stimulation and high expression of interleukin-1receptor-associated kinase-M (IRAK-M), indicating prior in vivo exposure to TLR-4 ligand(s). Furthermore, injection of LPS intraperitoneally increased T cell CD69 expression in pancreatic lymph node (PaLN), suggestive of T cell activation. Leakage of bacterial components such as endotoxins into the peritoneal cavity may contribute to auto-reactive T cell activation in the PaLN.
authors.affiliation: Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland.
authors.forename: R
authors.initials: R
authors.lastname: Emani
authors.forename: C
authors.initials: C
authors.lastname: Alam
authors.forename: S
authors.initials: S
authors.lastname: Pekkala
authors.forename: S
authors.initials: S
authors.lastname: Zafar
authors.forename: M R
authors.initials: MR
authors.lastname: Emani
authors.forename: A
authors.initials: A
authors.lastname: Hänninen
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D015551:Autoimmunity / Q000276:immunology*; D015153:Blotting, Western; D002478:Cells, Cultured; D005434:Flow Cytometry; D007274:Injections, Intraperitoneal; D053592:Interleukin-1 Receptor-Associated Kinases / Q000276:immunology / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000276:immunology*; D037181:Lectins, C-Type / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D064307:Microbiota / Q000276:immunology*; D010529:Peritoneal Cavity / Q000166:cytology / Q000382:microbiology / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology*; D013045:Species Specificity; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism; D014886:Weaning; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D053592:Interleukin-1 Receptor-Associated Kinases; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D000099192:CD69 Antigens; C507772:Irak3 protein, mouse