Gamma-delta T cell-mediated regulation of chemokine producing macrophages during Listeria monocytogenes infection-induced inflammation

Tramonti, D., Rhodes, K. A., Martin, N. G., Dalton, J. E., Andrew, E. and Carding, S. R. (2008) Gamma-delta T cell-mediated regulation of chemokine producing macrophages during Listeria monocytogenes infection-induced inflammation. The Journal of Pathology, 216 (2). pp. 262-270. ISSN 1096-9896

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Abstract

Infection of γδT cell-deficient (TcRδ−/−) mice with the intracellular bacterium Listeria monocytogenes (Lm) results in an exacerbated inflammatory response characterized by the accumulation of activated macrophages and necrotic liver lesions. Here we investigated whether changes in chemokine production by Lm-elicited macrophages contribute to this abnormal inflammatory response. In response to Lm infection, activated macrophages accumulate in the primary sites of infection in TcRδ−/− mice and express high amounts of mRNA encoding the chemokines CCL3 (MIP-1α), CCL4 (MIP-1β), CXCL2 (MIP-2) and CXCL10 (IP-10). In the infected tissues of TcRδ−/− the number of chemokine-synthesizing macrophages was higher than in wild-type (WT) mice, with the amount of MIP-1α and MIP-1β secreted by individual macrophages in the spleen of TcRδ−/− mice also being significantly higher than in WT mice. By contrast, protease activity and NO production in individual splenic macrophages of Lm-infected TcRδ−/− and WT mice were comparable. Pathogen-elicited macrophages in TcRδ−/− mice also expressed high levels of the CCL3 and CCL4 receptor, CCR5. In macrophage-γδT cell co-cultures, chemokine-producing macrophages were killed by cytotoxic Vγ1+ T cells in a Fas–FasL-dependent manner consistent with the high levels of chemokine-producing macrophages seen in infected TcRδ−/− mice being due to the absence of Vγ1+ T cells. Together these findings highlight the importance of γδT cells in regulating macrophage anti-microbial responses.

Item Type:	Article
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology
Depositing User:	EPrints Services
Date Deposited:	25 Nov 2010 11:13
Last Modified:	24 Sep 2024 09:27
URI:	https://ueaeprints.uea.ac.uk/id/eprint/15087
DOI:	10.1002/path.2412

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