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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. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]