Consistent with our findings, a previous study showed that the parasite numbers in the livers of CCR5−/− mice were higher than those of the C57BL/6 wild-type animals, while the parasite numbers were similar in other organs of the WT and CCR5−/− mice [27]. Therefore, TgCyp18-mediated CCL5 production might contribute to macrophage migration to the site of infection and the

Veliparib supplier transport of T. gondii-infected cells to the liver. Besides CCR5, CCL5 has been shown to interact with other receptors, including CCR3 and CCR1. Therefore, activation of CCR1- and CCR3-signaling may contribute to CCL5-mediated pathology during T. gondii infection. Hence, the chemokines up-regulated in CCR5−/− mice infected with RH-OE may play a crucial role in CCR5-independent macrophage migration. To test this idea in our study, the expression levels of chemokines related to macrophage migration were investigated. In vitro analysis showed that TgCyp18 increased the expression of CCL6 in a CCR5 independent manner. However, the in vivo data showed that a higher level of CCL6 was observed in the livers of the CCR5−/− mice infected RH-GFP at 3 dpi compared with those infected with RH-OE. Although we do not know the reason for the difference between the in vitro and in vivo data, it is possible that CCL6 expression might have been induced before 3 dpi in the livers of the CCR5−/−

mice infected with RH-OE. It is interesting to note that CCL2 expression was slightly increased in macrophages treated with recombinant TgCyp18. Moreover, the expression levels of CCL2 Hydroxylase inhibitor and CXCL10 were significantly higher at 3 dpi in the livers of CCR5−/− mice infected with RH-OE compared with the uninfected mice. Thus, TgCyp18-mediated production of CCL2 and CXCL10 in the liver may trigger transport

of T. gondii-infected macrophages via a CCR2 and CXCR3-dependent mechanism, respectively. CCR2−/− mice have profound defects in monocyte recruitment although constitutive trafficking remains unaffected [28]. CCR2−/− mice or CCL2−/− mice failed to Bay 11-7085 recruit Gr1+ inflammatory monocytes, which are required for mucosal resistance to T. gondii[29], or to control systemic toxoplasmosis by intraperitoneal infection [30]. Furthermore, another group reported that the CXCR3 ligands, CXCL9, CXCL10 and CXCL11, were induced markedly at the levels in the spleen, lung, and liver following infection with T. gondii[27]. Induction of these chemokines was similar in WT and CCR5−/− mice up to day 5 [27]. CXCL10 is required to maintain T-cell check details populations and to control parasite replication during chronic ocular toxoplasmosis [31]. These results suggest that CCR2 and CCL2, or CXCR3 and its ligands, play a crucial role in cell migration and control of T. gondii infection. Diana et al. [32] showed that a T. gondii excreted-secreted antigen induced recruitment and migration of human DCs in a CCR5-dependent fashion. Other studies in mice have reported that T.