Simian immunodeficiency virus–induced mucosal interleukin-17 deficiency promotes Salmonella dissemination from the gut
- 23 March 2008
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Medicine
- Vol. 14 (4), 421-428
- https://doi.org/10.1038/nm1743
Abstract
Salmonella typhimurium causes a localized enteric infection in immunocompetent individuals, whereas HIV-infected individuals develop a life-threatening bacteremia. Here we show that simian immunodeficiency virus (SIV) infection results in depletion of T helper type 17 (TH17) cells in the ileal mucosa of rhesus macaques, thereby impairing mucosal barrier functions to S. typhimurium dissemination. In SIV-negative macaques, the gene expression profile induced by S. typhimurium in ligated ileal loops was dominated by TH17 responses, including the expression of interleukin-17 (IL-17) and IL-22. TH17 cells were markedly depleted in SIV-infected rhesus macaques, resulting in blunted TH17 responses to S. typhimurium infection and increased bacterial dissemination. IL-17 receptor–deficient mice showed increased systemic dissemination of S. typhimurium from the gut, suggesting that IL-17 deficiency causes defects in mucosal barrier function. We conclude that SIV infection impairs the IL-17 axis, an arm of the mucosal immune response preventing systemic microbial dissemination from the gastrointestinal tract.This publication has 48 references indexed in Scilit:
- Rapid Onset of Intestinal Epithelial Barrier Dysfunction in Primary Human Immunodeficiency Virus Infection Is Driven by an Imbalance between Immune Response and Mucosal Repair and RegenerationJournal of Virology, 2008
- The Capsule Encoding theviaBLocus Reduces Interleukin-17 Expression and Mucosal Innate Responses in the Bovine Intestinal Mucosa during Infection withSalmonella entericaSerotype TyphiInfection and Immunity, 2007
- The Interleukin-22/STAT3 Pathway Potentiates Expression of Inducible Nitric-oxide Synthase in Human Colon Carcinoma CellsOnline Journal of Public Health Informatics, 2007
- Microbial translocation is a cause of systemic immune activation in chronic HIV infectionNature Medicine, 2006
- Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptidesThe Journal of Experimental Medicine, 2006
- Interleukin-17 is a potent immuno-modulator and regulator of normal human intestinal epithelial cell growthBiochemical and Biophysical Research Communications, 2005
- A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17Nature Immunology, 2005
- Interleukin 17–producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineagesNature Immunology, 2005
- Divergent roles of IL-23 and IL-12 in host defense against Klebsiella pneumoniae The Journal of Experimental Medicine, 2005
- Primary Acute Simian Immunodeficiency Virus Infection of Intestinal Lymphoid Tissue Is Associated with Gastrointestinal DysfunctionThe Journal of Infectious Diseases, 1994