Mesenchymal cell-specific MyD88 signaling promotes systemic dissemination of salmonella typhimurium via inflammatory monocytes Academic Article Article uri icon

Overview

MeSH Major

  • Asymptomatic Diseases
  • Cerebrovascular Disorders
  • Coronary Artery Disease
  • Peripheral Arterial Disease

abstract

  • Copyright © 2017 by The American Association of Immunologists, Inc. Enteric pathogens including Salmonella enteric serovar Typhimurium can breach the epithelial barrier of the host and spread to systemic tissues. In response to infection, the host activates innate immune receptors via the signaling molecule MyD88, which induces protective inflammatory and antimicrobial responses. Most of these innate immune responses have been studied in hematopoietic cells, but the role of MyD88 signaling in other cell types remains poorly understood. Surprisingly, we found that Dermo1-Cre;Myd88fl/fl mice with mesenchymal cell-specific deficiency of MyD88 were less susceptible to orogastric and i.p. S. Typhimurium infection than their Myd88fl/fl littermates. The reduced susceptibility of Dermo1-Cre;Myd88fl/fl mice to infection was associated with lower loads of S. Typhimurium in the liver and spleen. Mutant analyses revealed that S. Typhimurium employs its virulence type III secretion system 2 to promote its growth through MyD88 signaling pathways in mesenchymal cells. Inflammatory monocytes function as a major cell population for systemic dissemination of S. Typhimurium. Mechanistically, mesenchymal cell-specific MyD88 signaling promoted CCL2 production in the liver and spleen and recruitment of inflammatory monocytes to systemic organs in response to S. Typhimurium infection. Consistently, MyD88 signaling in mesenchymal cells enhanced the number of phagocytes including Ly6ChiLy6G2 inflammatory monocytes harboring S. Typhimurium in the liver. These results suggest that S. Typhimurium promotes its systemic growth and dissemination through MyD88 signaling pathways in mesenchymal cells. Enteric pathogens including Salmonella enteric serovar Typhimurium can breach the epithelial barrier of the host and spread to systemic tissues. In response to infection, the host activates innate immune receptors via the signaling molecule MyD88, which induces protective inflammatory and antimicrobial responses. Most of these innate immune responses have been studied in hematopoietic cells, but the role of MyD88 signaling in other cell types remains poorly understood. Surprisingly, we found that Dermo1-Cre;Myd88fl/fl mice with mesenchymal cell-specific deficiency of MyD88 were less susceptible to orogastric and i.p. S. Typhimurium infection than their Myd88fl/fl littermates. The reduced susceptibility of Dermo1-Cre;Myd88fl/fl mice to infection was associated with lower loads of S. Typhimurium in the liver and spleen. Mutant analyses revealed that S. Typhimurium employs its virulence type III secretion system 2 to promote its growth through MyD88 signaling pathways in mesenchymal cells. Inflammatory monocytes function as a major cell population for systemic dissemination of S. Typhimurium. Mechanistically, mesenchymal cell-specific MyD88 signaling promoted CCL2 production in the liver and spleen and recruitment of inflammatory monocytes to systemic organs in response to S. Typhimurium infection. Consistently, MyD88 signaling in mesenchymal cells enhanced the number of phagocytes including Ly6ChiLy6G2 inflammatory monocytes harboring S. Typhimurium in the liver. These results suggest that S. Typhimurium promotes its systemic growth and dissemination through MyD88 signaling pathways in mesenchymal cells.

publication date

  • August 15, 2017

Research

keywords

  • Academic Article

Identity

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.1601527

PubMed ID

  • 28674182

Additional Document Info

start page

  • 1362

end page

  • 1371

volume

  • 199

number

  • 4