Monocyte trafficking to hepatic sites of bacterial infection is chemokine independent and directed by focal intercellular adhesion molecule-1 expression.
Recruitment of CCR2(+)Ly6C(high) monocytes to sites of infection is essential for efficient clearance of microbial pathogens. Although CCR2-mediated signals promote monocyte emigration from bone marrow, the contribution of CCR2 to later stages of monocyte recruitment remains unresolved. In this article, we show that CCR2 deficiency markedly worsens hepatic Listeria monocytogenes infection because Ly6C(high) monocytes are retained in the bone marrow. Intravenously transferred, CCR2-deficient Ly6C(high) monocytes traffic normally to hepatic foci of infection and contribute to bacterial clearance. Pertussis toxin treatment of adoptively transferred monocytes does not impair their intrahepatic trafficking, suggesting that chemokine signaling, once CCR2(+)Ly6C(high) monocytes emigrate from the bone marrow, is not required for monocyte localization to sites of bacterial infection in the liver. Expression of ICAM-1 is induced in close proximity to foci of bacterial infection in the liver, including on CD31(+) endothelial cells, and blockade of CD11b and CD44 diminishes monocyte localization to these hepatic foci. Our studies demonstrated that Ly6C(high) monocyte recruitment from the bloodstream to the L. monocytogenes-infected liver does not require chemokine receptor-mediated signals but instead is principally dependent on integrin- and extracellular matrix-mediated monocyte adhesion.
Shi
Chao
C
Infectious Disease Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Velázquez
Peter
P
Hohl
Tobias M
TM
Leiner
Ingrid
I
Dustin
Michael L
ML
Pamer
Eric G
EG
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D002469:Cell Separation; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology* / Q000378:metabolism; D008089:Listeria monocytogenes / Q000276:immunology; D008088:Listeriosis / Q000276:immunology* / Q000378:metabolism; D008099:Liver / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008822:Mice, Transgenic; D009000:Monocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D054390:Receptors, CCR2 / Q000276:immunology / Q000378:metabolism
C515335:Ccr2 protein, mouse; D054390:Receptors, CCR2; D018799:Intercellular Adhesion Molecule-1