Title | Mesenchymal Cell-Specific MyD88 Signaling Promotes Systemic Dissemination of via Inflammatory Monocytes. |
Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | Kim D, Seo S-U, Zeng MY, Kim W-U, Kamada N, Inohara N, Nunez G |
Journal | J Immunol |
Volume | 199 |
Issue | 4 |
Pagination | 1362-1371 |
Date Published | 2017 08 15 |
ISSN | 1550-6606 |
Keywords | Animals, Antigens, Ly, Bacterial Load, Chemokine CCL2, Immunity, Innate, Liver, Mice, Mice, Inbred C57BL, Monocytes, Myeloid Differentiation Factor 88, Salmonella Infections, Animal, Salmonella typhimurium, Signal Transduction, Spleen, Type III Secretion Systems |
Abstract | Enteric pathogens including serovar 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 mice with mesenchymal cell-specific deficiency of MyD88 were less susceptible to orogastric and i.p. infection than their littermates. The reduced susceptibility of mice to infection was associated with lower loads of in the liver and spleen. Mutant analyses revealed that 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 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 infection. Consistently, MyD88 signaling in mesenchymal cells enhanced the number of phagocytes including Ly6CLy6G inflammatory monocytes harboring in the liver. These results suggest that promotes its systemic growth and dissemination through MyD88 signaling pathways in mesenchymal cells. |
DOI | 10.4049/jimmunol.1601527 |
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Alternate Journal | J. Immunol. |
PubMed ID | 28674182 |
PubMed Central ID | PMC5548622 |
Grant List | R01 AI063331 / AI / NIAID NIH HHS / United States R01 DK061707 / DK / NIDDK NIH HHS / United States R01 DK091191 / DK / NIDDK NIH HHS / United States T32 HL007517 / HL / NHLBI NIH HHS / United States |