International Immunology, Vol 10, 757-765, Copyright © 1998 by Oxford University Press
IE Flesch, J Barsig and SH Kaufmann
During inflammatory processes the infected macrophage is a rich source of
chemokines which induce infiltration of leukocytes to the site of
infection. We investigated the regulation of chemokine production by murine
macrophages in response to infection with the intracellular bacterial
pathogen, Listeria monocytogenes. As a source of quiescent macrophages,
murine bone marrow-derived macrophages (BMM) cultured under serum-free
conditions were used. With RT-PCR, we detected induction of RNA message for
the 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-detectable
MIP-1alpha, MIP-2 and KC protein was induced by infection with L.
monocytogenes. In contrast, L. monocytogenes infection of BMM alone failed
to induce considerable expression of monocyte chemoattractant protein
(MCP)-1 at the mRNA or protein level, but co-treatment with IFN-gamma was
necessary. Release of infection- triggered MIP-2, MIP-1alpha and KC was
negatively regulated by IFN- gamma. Similarly, IL-4 stimulated MCP-1
release by infected macrophages but reduced production of MIP-1alpha, MIP-2
and KC. IL-10 turned out to be a general deactivator in terms of macrophage
chemokine production. IL-13 had no effect on MIP-1alpha, MIP-2 and KC
production by infected BMM, but slightly reduced MCP-1 release. By using
IFN-gamma and IL-4 gene deletion mutant mice, in vivo regulation of these
chemokines by IL- 4 and IFN-gamma in listeriosis was studied. In summary,
our results show that chemokines are produced by macrophages infected with
L. monocytogenes, and that chemokine release is differentially regulated by
the macrophage modulators IFN-gamma, IL-4, IL-10 and IL-13.
ARTICLES
Differential chemokine response of murine macrophages stimulated with cytokines and infected with Listeria monocytogenes
Department of Immunology, University of Ulm, Germany.
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