Divergent expression of inflammatory dermal chemokines in cutaneous leishmaniasis.
Human leishmaniasis is caused by protozoan Leishmania (L.) parasites and comprises a heterogeneous group of clinical appearances ranging from visceral to cutaneous leishmaniasis. In the New World, L. mexicana mediates American cutaneous leishmaniasis, one of the most common forms of this disease. Two different disease progressions can be observed: (i) self-healing localized cutaneous leishmaniasis (LCL) and (ii) progressive diffuse cutaneous leishmaniasis (DCL). These different forms are associated with a T helper 1 (Th1) or Th2 response, respectively, and are additionally characterized by opposing dermal chemokine profiles. Lesions of LCL show high expression of CCL2/MCP-1, CXCL9/MIG, CXCL10/IP-10 and only low amounts of CCL3/MIP-1alpha. In contrast, lesions of chronic DCL are dominated by the expression of CCL3/MIP-1alpha. This finding implies that CCL2/MCP-1 contributes to the healing process. Indeed, CCL2/MCP-1 induces leishmanicidal activities in human monocytes in contrast to CCL3/MIP-1alpha. This effect is enhanced by interferon-gamma and abrogated by interleukin-4. In the murine model of leishmaniasis, the impact of CCL2/MCP-1 is well documented. Normally resistant mice become susceptible for Leishmania infections if CCR2, the receptor for CCL2/MCP-1, is knocked out. Based on this evidence, we propose that tissue specific expression of these small molecules actively regulates cell traffic and tissue localization of effector cells and, additionally, has direct immunological effects.
Ritter
Uwe
U
Nikolaus-Fiebiger Zentrum für Molekulare Medizin, University of Erlangen-Nürnberg, Erlangen, Germany. uritter@molmed.uni-erlangen.de
Körner
Heinrich
H
D000818:Animals; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology / Q000469:parasitology; D020405:Dermis / Q000276:immunology / Q000469:parasitology*; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000469:parasitology; D007891:Leishmania / Q000254:growth & development / Q000472:pathogenicity; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000473:pathology; D008018:Life Cycle Stages; D018448:Models, Immunological
D018925:Chemokines