LEISHMANIA-MAJOR - PROMASTIGOTES INDUCE EXPRESSION OF A SUBSET OF CHEMOKINE GENES IN MURINE MACROPHAGES

Recent studies suggest that Leishmania major promastigotes infect cult ured macrophages in a stealthy fashion, activating little or no host g ene expression and often interfering with the host's ability to respon d to further stimulation. Here we examined macrophage transcription at early times following infection, when virulent parasites must execute steps required for survival. Stationary-phase promastigotes induced r apid and transient expression of transcripts of the chemokines JE (hum an MCAF/MCP-1) and KC (human GRO) in bone marrow-derived macrophages f rom BALB/c mice. JE and KC expression rose four- to sixfold shortly af ter infection and returned to uninduced levels by 4-24 hr. In contrast , chemokines MIP-1 alpha, C10, and RANTES were not induced, nor were T GF-beta, IL-10, IL-12, or i-NOS. Chemokine induction did not occur fol lowing ingestion of latex beads, implicating a parasite-specific stimu lus. Elevated expression of a subset of chemokines is the earliest kno wn transcriptional response of macrophages to L. major infection and p otentially may provide a signal for the initiation of downstream immun ological responses which occur in vivo, such as cytokine induction and chemotaxis of monocytes and macrophages. Thus, Leishmania has a remar kable ability to take an active role in either inducing or preventing the expression of distinct sets of host genes during macrophage invasi on and successful intracellular parasitism. (C) 1997 Academic Press.