| Abstract: |
Chemokine receptor-mediated recruitment of inflammatory cells is essential for innate immune defense against microbial infection. Recruitment of Ly6C high inflammatory monocytes from bone marrow to sites of microbial infection is dependent on CCR2, a chemokine receptor that responds to MCP-1 and MCP-3. Although CCR2-/- mice are markedly more susceptible to Listeria monocytogenes infection than are wild-type mice, MCP-1-/- mice have an intermediate phenotype, suggesting that other CCR2 ligands contribute to antimicrobial defense. Herein, we show that L. monocytogenes infection rapidly induces MCP-3 in tissue culture macrophages and in serum, spleen, liver, and kidney following in vivo infection. Only cytosol invasive L. monocytogenes induce MCP-3, suggesting that cytosolic innate immune detection mechanisms trigger chemokine production. MCP-3-/- mice clear bacteria less effectively from the spleen than do wild-type mice, a defect that correlates with diminished inflammatory monocyte recruitment. MCP-3 -/- mice have significantly fewer Ly6Chigh monocytes in the spleen and bloodstream, and increased monocyte numbers in bone marrow. MCP-3-/- mice, like MCP-1-/- mice, have fewer TNF- and inducible NO synthase-pro-ducing dendritic cells (Tip-DCs) in the spleen following L. monocytogenes infection. Our data demonstrate that MCP-3 and MCP-1 provide parallel contributions to CCR2-mediated inflammatory monocyte recruitment and that both chemokines are required for optimal innate immune defense against L. monocytogenes infection. Copyright © 2008 by The American Association of Immunologists, Inc. |
| Keywords: |
nonhuman; flow cytometry; animal cell; mouse; phenotype; animal; metabolism; mouse mutant; animals; mice; animal tissue; cells, cultured; spleen; protein protein interaction; inflammation; mice, mutant strains; in vivo study; wild type; enzyme linked immunosorbent assay; liver; immunology; kidney; cell culture; innate immunity; bone marrow cell; enzyme-linked immunosorbent assay; monocyte; monocytes; monocyte chemotactic protein 3; macrophage; macrophages; chemokine receptor ccr2; receptors, ccr2; monocyte chemotactic protein 1; listeriosis; listeria monocytogenes; neutrophil chemotaxis; chemokine ccl2; chemotaxis, leukocyte; listeria infections; chemokine receptor; tumor necrosis factor; inducible nitric oxide synthase; ccr2 protein, mouse; macrophage activation; chemokine ccl7
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