Molecular immunological analysis of early resistance existed in susceptible mice to protozoan infection.

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To understand the immunomodulatory roles of neutrophils in Leishmania major infection, we examined-the expression of cytokine and/or chemokine mRNAs from neutrophils of the infected resistant C3H/HeJ and susceptible BALB/c mice. We also examined the effects of neutrophil depletion on the expression of cytokine mRNAs by peritoneal macrophages and draining lymph nodes cells and on the footpad lesions and parasite burdens in these mice. Neutrophils from resistant C3H/HeJ but not from susceptible BALB/c mice expressed mRNAs for IL-12p40, IFN-1γ, TNF-α, and a Th1 cell chemoattractive chemokine, monikine induced by IFN-γ (MIG). Neutrophil depletion of the resistant mice reduced the expression of IFN-γ and TNF-α mRNAs in peritoneal macrophages, but did not affected the expression of IL-12p40 mRNAs in draining lymph nodes and the growth of footpad lesions. On the other hand, neutrophil depletion of susceptible BALB/c mice did not affect the expression of TNF-α and a Th2 cell chemoattractive chemokine, monocyte derived chemokine (MDC) in peritoneal macrophages, but induced the early stage expression of IL-4 mRNA in draining lymph nodes cells and exacerbated the footpad lesions and increased the parasite burden. Our results suggest that even in susceptible BALB/c but not in C3H/HeJ mice there is a certain resistance requiring neutrophils at the early stage of infection.