major infection changed

neither the cellular and humoral response to S. ratti nor the clearance of infection although 2 days of pre-existing L. major infection readily suppressed S. ratti-induced Th2 response (Figure 2b). We analysed the outcome of infection and the nature of immune response in mice co-infected with L. major and S. ratti, i.e. parasites that elicit and are efficiently cleared by Th1 and Th2 immune responses, respectively. We show that a pre-existing S. ratti infection did not interfere with the control of L. major high-dose or low-dose infections. Also, the generation of a protective memory response was not affected in co-infected mice. In line with these findings, neither the local L. major-specific Th1 response in the popLN

nor the systemic humoral response as indicated by L. major-specific Ig in the serum was suppressed by S. ratti co-infection. In contrast, we observed increased proliferation Apoptosis inhibitor and IFN-γ production in popLN of co-infected mice responding to anti-CD3 and SLA stimulation. GSK2126458 mouse We observed also spontaneous proliferation and cytokine secretion in the absence of stimulating agents in the popLN, thus reflecting a generalized activation of lymphocytes. As we set both experimental infections into the same footpad, the popLN that we investigated drained tissue containing both L. major and migrating S. ratti larvae. Therefore, we argue that we did not observe a compartmentalization of immune responses to parasites residing at distinct sites as was shown for L. sigmodontis and L. major co-infection (22). In our co-infection system,

the L. major-specific Th1 response apparently dominated the local lymphocyte differentiation. Infection with S. ratti is resolved within 3 to 4 weeks and displays a very short period, i.e. 3–5 days of maximal Th2 response and reciprocal suppression of Th1 response as we demonstrated by kinetic studies (10). It is conceivable that the transient nature of this nematode infection explained the missing impact on subsequent L. major infection. In line with our findings, efficient control of L. major infection was reported in C57BL/6 mice co-infected with Nippostrongylus brasiliensis that is expelled in the context of a Th2 response (23). Unchanged or even accelerated resolution of L. major Rapamycin infection was reported in C57BL/6 mice with pre-existing L. sigmodontis infection (22). Furthermore, an increased IFN-γ production in response to L. major antigen and in the absence of stimulation was described in L. sigmodontis/L. major co-infected mice, strongly resembling the increased pro-inflammatory response we observed in the popLN in S. ratti/L. major co-infected mice. Although L. sigmodontis infection is long lasting in BALB/c mice, the larvae do not proceed beyond the fourth stage and never reach the patency in the C57BL6 mice used in the cited study (22,24,25).