MyD88 and type I interferon receptor-mediated chemokine induction and monocyte recruitment during Listeria monocytogenes infection Journal Article


Authors: Jia, T.; Leiner, I.; Dorothee, G.; Brandl, K.; Pamer, E. G.
Article Title: MyD88 and type I interferon receptor-mediated chemokine induction and monocyte recruitment during Listeria monocytogenes infection
Abstract: Monocytes play a central role in defense against infection, but the mechanisms promoting monocyte recruitment and activation remain incompletely defined. Defense against Listeria monocytogenes, an intracellular bacterial pathogen, requires in vivo MCP-1 induction and CCR2-dependent recruitment of Ly6C<sup>high</sup> monocytes from bone marrow to sites of infection. Herein, we demonstrate that infection of bone marrow-derived macrophages with virulent L. monocytogenes induces MCP-1 expression in two phases. The first phase is rapid, induces low-level production of MCP-1, and is dependent on TLR/MyD88 signaling. The second phase promotes prolonged, higher level MCP-1 secretion and is dependent on signaling via the type I IFN receptor (IFNAR). Although attenuated L. monocytogenes strains that remain confined to the phagosome trigger TLR/MyD88-mediated signals and induce low-level MCP-1 expression, only cytosol-invasive bacteria promote IFNAR-dependent MCP-1 expression. In vivo, defi-ciency of either MyD88 or IFNAR signaling does not impair early monocyte emigration from bone marrow and recruitment to infected spleen. Loss of both MyD88 and IFNAR-mediated MCP-1 induction, however, results in deficient Ly6Chigh monocyte recruitment and increased susceptibility to L. monocytogenes infection. Our studies demonstrate that distinct but partially overlapping signal transduction pathways provide redundancy that ensures optimal monocyte recruitment to sites of microbial infection. Copyright © 2009 by The American Association of Immunologists, Inc.
Keywords: signal transduction; controlled study; protein expression; nonhuman; mouse; animal; mouse mutant; animals; mice; mice, knockout; bone marrow cells; bone marrow; spleen; animal experiment; animal model; bacterial strain; physiology; biosynthesis; immunology; chemokine; cell migration; protein induction; cytokine production; bone marrow cell; monocyte; monocytes; microbiology; macrophage; macrophages; cytokine release; phagosome; myeloid differentiation factor 88; toll like receptor; interferon receptor; monocyte chemotactic protein 1; alpha beta interferon receptor; ccl2 protein, mouse; myd88 protein, mouse; cytosol; listeriosis; listeria monocytogenes; neutrophil chemotaxis; chemokine ccl2; chemokines; chemotaxis, leukocyte; listeria infections; receptor, interferon alpha-beta
Journal Title: Journal of Immunology
Volume: 183
Issue: 2
ISSN: 0022-1767
Publisher: The American Association of Immunologists, Inc  
Date Published: 2009-07-15
Start Page: 1271
End Page: 1278
Language: English
DOI: 10.4049/jimmunol.0900460
PUBMED: 19553532
PROVIDER: scopus
PMCID: PMC2735446
DOI/URL:
Notes: --- - "Cited By (since 1996): 4" - "Export Date: 30 November 2010" - "CODEN: JOIMA" - "Source: Scopus"
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MSK Authors
  1. Eric Pamer
    283 Pamer
  2. Ingrid Leiner
    49 Leiner
  3. Ting Jia
    6 Jia