Skip to main content

Research Repository

Advanced Search

Peritoneal cavity is a route for gut-derived microbial signals to promote autoimmunity in non-obese diabetic mice

Emani, R.; Alam, C.; Pekkala, S.; Zafar, S.; Emani, M.R.; H�nninen, A.


R. Emani

S. Pekkala

S. Zafar

M.R. Emani

A. H�nninen


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.

Journal Article Type Article
Acceptance Date Nov 10, 2014
Online Publication Date Jan 20, 2015
Publication Date 2015-02
Deposit Date May 26, 2022
Journal Scandinavian journal of immunology
Print ISSN 0300-9475
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 81
Issue 2
Pages 102-109
Public URL