Chemokines, natural killer cells and granulocytes in the early course of Leishmania major infection in mice

In the present study the early recruitment of leukocytes into the infected skin and into the draining lymph node (LN) was investigated after subcutane ous infection of mice with Leishmania major promastigotes. Flow cytometric analysis of cells recovered from the infected skin revealed that GR-1(+) gr anulocytes were present as early as 10 h after infection, thus representing the first leukocyte population to be recruited to the site of infection. T he migration of granulocytes was shown to be associated with a rapid mRNA e xpression of the neutrophil-attracting chemokine KC in the infected skin. M oreover, L. major promastigotes were found to produce factor(s) that are ch emotactic for human neutrophils in vitro. Experiments with human neutrophil s revealed that these cells are able to phagocytose the parasites. Natural killer (NK) cells appeared at the site of infection 24 h after infection. T he migration of NK cells in resistant mice was found to correlate with the expression of the NK cell-activating chemokine IP-10. Treatment of suscepti ble BALB/c mice with recombinant mouse IP-10 resulted in a significantly in creased NK cell cytotoxic activity in the draining LN. These data suggest t hat both the early chemokine gene expression and the production of chemotac tic factors by the parasites themselves regulate the site-directed migratio n and activation of cells of the innate immune response, and suggest a role of chemotactic factors in the early defense against the parasites.