LE/shmania major. Infection of human monocytes selectively induces production of chemokines

Leishmania are obligate intracellular parasites of monocytes, that may cause systemic disease or skin manifestations in humans. Leishmanial lesions are constituted of infected cells surrounded by macrophages interspersed with lymphocytes and polymorphonuclear cells (PMN). Since leukocyte infiltration is a common event of any inflammatory response, and monocytes are a major source of cytokines with chemotactic properties for PMN (IL-8) and for monocytes (MCAF), we asked whether L major might induce monocytes production of chemokines. Human monocytes were infected with L major ; supematants, that were collected after 18 hours of incubation, had chemotactic properties for monocytes as well as for PMN. Anti-MCAF Ig neutralized up to 52% of the monocyte chemotactic activity while anti-IL-8 neutralized up to 73% of the PMN chemotactic activity. Then we investigated whether chemokines expression by Le/shmama-infected-monocytes were accompanied with production of proinflammatory cytokines. TNF-o and IL-1II were detected at concentrations about 20 times lower than IL-8 in supematants derived from J.e/sftmama-infected monocytes while LPS was effective to the same extent to induce TNF-a, IL-1S and IL-8 secretion. These results suggest that L. major might induce a selective activation of monocytes for chemokines production to determine the recruitment of host cells permissive to the parasite.