Schistosomiasis delays lesion resolution during Leishmania major infection by impairing parasite killing by macrophages

Abstract

Infection of mice with Schistosoma mansoni delays the resolution of cutaneous lesions and parasitaemia during Leishmania major infection. In contrast, L. major infection does not appear to alter the course of schistosomiasis. Analysis of the cytokine responses in the draining lymph nodes (LN) indicates that, while L. major infection had no effect on schistosome-specific interleukin (IL)-4 production by mesenteric LN (MLN) cells, coinfection with S. mansoni resulted in decreased leishmania-induced interferon (IFN)-gamma, tumour necrosis factor-alpha and nitric oxide production by popliteal LN (PLN) cells 4 weeks after L. major infection. In addition, PLN cells produced higher levels of IL-4 4 weeks after L. major infection in coinfected mice. Finally, IFN-gamma-stimulated macrophages isolated from S. mansoni-infected mice were impaired in their ability to kill L. major after in vitro infection. These results suggest that pre-existence of a strong Th2 response-dominated infection can alter the responses to Th1-inducing pathogens at peripheral sites and impair Th1-mediated effector functions.