LeishmaniaPromastigotes Release a Granulocyte Chemotactic Factor and Induce Interleukin-8 Release but Inhibit Gamma Interferon-Inducible Protein 10 Production by Neutrophil Granulocytes

Abstract

Recent data from our laboratory suggest that neutrophil granulocytes (polymorphonuclear leukocytes [PMN]) can serve as host cells forLeishmania majorin the early phase of infection. In line with these findings, an early influx of PMN to the infected tissues was shown by others to be associated with susceptibility to infection withL. major. The mechanisms underlying the initial PMN recruitment to the site of infection is poorly understood. In the present study we investigated whetherLeishmaniacan influence PMN migration. Supernatants ofLeishmaniapromastigotes were tested for their chemotactic activity using an in vitro chemotaxis assay. AllLeishmaniaspecies tested (L. major,L. aethiopica, andL. donovani) displayed a marked chemotactic effect on human PMN. However, no effect on the migration of macrophages and NK cells was observed. Checkerboard analysis revealed that the observed PMN migration was due to chemotaxis rather than chemokinesis. Most of the chemotactic activity was found in fractions containing molecules with sizes between 10 and 50 kDa. Pretreatment of PMN withN-formyl-methionyl-leucyl-phenylalanine blocked the chemotactic activity ofLeishmaniasupernatants up to 75%. In addition, we found that leishmanial contact induced the release of interleukin-8 (IL-8) and inhibited the production of gamma interferon-inducible protein 10 (IP-10) by PMN. These data suggest that infection withLeishmaniapromastigotes leads to PMN accumulation via the production of a chemotactic factor by the parasites, and this effect is amplified by the induction of IL-8 production in PMN. On the other hand, the inhibition of IP-10 production can lead to prevention of NK cell activation.