Differential chemokine response of murine macrophages stimulated with cytokines and infected with Listeria monocytogenes

During inflammatory processes the infected macrophage is a rich source ofchemokines which induce infiltration of leukocytes to the site ofinfection. We investigated the regulation of chemokine production by murinemacrophages in response to infection with the intracellular bacterialpathogen, Listeria monocytogenes. As a source of quiescent macrophages,murine bone marrow-derived macrophages (BMM) cultured under serum-freeconditions were used. With RT-PCR, we detected induction of RNA message forthe chemokines macrophage inflammatory protein (MIP)-2, KC, MIP-1alpha,MIP-1beta, IFN-gamma-inducible protein- 10 and RANTES in L.monocytogenes-infected macrophages. Accordingly, ELISA-detectableMIP-1alpha, MIP-2 and KC protein was induced by infection with L.monocytogenes. In contrast, L. monocytogenes infection of BMM alone failedto induce considerable expression of monocyte chemoattractant protein(MCP)-1 at the mRNA or protein level, but co-treatment with IFN-gamma wasnecessary. Release of infection- triggered MIP-2, MIP-1alpha and KC wasnegatively regulated by IFN- gamma. Similarly, IL-4 stimulated MCP-1release by infected macrophages but reduced production of MIP-1alpha, MIP-2and KC. IL-10 turned out to be a general deactivator in terms of macrophagechemokine production. IL-13 had no effect on MIP-1alpha, MIP-2 and KCproduction by infected BMM, but slightly reduced MCP-1 release. By usingIFN-gamma and IL-4 gene deletion mutant mice, in vivo regulation of thesechemokines by IL- 4 and IFN-gamma in listeriosis was studied. In summary,our results show that chemokines are produced by macrophages infected withL. monocytogenes, and that chemokine release is differentially regulated bythe macrophage modulators IFN-gamma, IL-4, IL-10 and IL-13.