REGIONAL DIFFERENCES IN THE CELLULAR IMMUNE-RESPONSE TO EXPERIMENTAL CUTANEOUS OR VISCERAL INFECTION WITH LEISHMANIA-DONOVANI

Infection with the protozoan Leishmania donovani can cause serious vis ceral disease or subclinical infection in humans, To better understand the pathogenesis of this dichotomy, we have investigated the host cel lular immune response to cutaneous or visceral infection in a murine m odel. Mice infected in the skin del eloped no detectable visceral para sitism, whereas intravenous inoculation resulted in hepatosplenomegaly and an increasing visceral parasite burden, Spleen cells from mice wi th locally controlled cutaneous infection showed strong parasite-speci fic proliferative and gamma interferon (IFN-gamma) responses, but sple en cells from systemically infected mice were unresponsive to parasite antigens, The in situ expression of IFN-gamma, interleukin-4 (IL-4), IL-10, IL-12, and inducible nitric oxide synthase (iNOS) mRNAs was det ermined in the spleen, draining lymph node (LN), and cutaneous site of inoculation, There was considerably greater expression of IPN-gamma a nd IL-12 p40 mRNAs in the LN draining a locally controlled cutaneous i nfection than in the spleen following systemic infection, Similarly, t here was a high level of IFN-gamma production by LN cells following su bcutaneous infection but no IFN-gamma production by spleen cells follo wing systemic infection, Splenic IL-4 expression was transiently incre ased early after systemic infection, but splenic IL-IO transcripts inc reased throughout the course of visceral infection, IL-4 and IL-10 mRN As were also increased in the LN following cutaneous infection, iNOS m RNA was detected earlier in the LN draining a cutaneous site of infect ion compared to the spleen following systemic challenge, Thus, locally controlled cutaneous infection was associated with antigen-specific s pleen cell responsiveness and markedly increased levels of IFN-gamma, IL-12, and iNOS mRNA in the draining LN. Progressive splenic parasitis m was associated with an early IL-4 response, markedly increased IL-10 but minimal IL-12 expression, and delayed expression of iNOS.