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This Article Full Text (PDF) All Versions of this Article: jimmunol.0900460v1 183/2/1271    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Jia, T. Articles by Pamer, E. G. PubMed PubMed Citation Articles by Jia, T. Articles by Pamer, E. G. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Substance via MeSH Medline Plus Health Information Listeria Infections

MyD88 and Type I Interferon Receptor-Mediated Chemokine Induction and Monocyte Recruitment During Listeria monocytogenes Infection¹

Ting Jia^*,, Ingrid Leiner^*, Guillaume Dorothee, Katharina Brandl and Eric G. Pamer^*,,2

*Infectious Diseases Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021; Program in Immunology and Microbial Pathogenesis, Weill Graduate School of Medical Sciences of Cornell University, New York, NY 10065; INSERM/UPMC UMRS 893, Eq. No.11, Immune System and Conformational Diseases, Hôpital Saint-Antoine, Paris, France; Department of Genetics, The Scripps Research Institute, La Jolla, California 92037

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^high 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, deficiency 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 Ly6C^high 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.

² Address correspondence and reprint requests to Dr. Eric G. Pamer, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 9, New York, NY 10021. E-mail address: pamere{at}mskcc.org

¹ This work was supported by the National Institutes of Health (R37AI039031, to E.G.P.) and a Feodor-Lynen postdoc fellowship from Humboldt foundation (to K.B.).