Transforming growth factor-ß in tegumentary leishmaniasis

RESUMO

1. The course of infection with the protozoan parasite Leishmania is determined in part by its early replication in macrophages, the exclusive host cells for these organisms. Resistance to and recovery from leishmanial infection is related to cell-mediated immune responses in all forms of human and murine leishmaniasis. 2. Factors contributing to the early inhibition or proliferation of Leishmania are poorly understood, but cytokines such as IFNÔ, IL-10 or transforming growth factor ß (TGF-ß) are known to influence the replication of Leishmania in macrophages. 3. TGF-ß is a multipotential cytokine with diverse effects on cells of the immune system, including down-regulation of certain macrophage functions. Infection of murine or human macrophages by Leishmania induces the production of active TGF-ß. Recombinant TGF-ß added to murine or human macrophage cultures leads to increased intracellular replication of Leishmania. Exogenous TGF-ß administered in vivo promotes enhancement of infection, whereas its neutralization by monoclonal antibodies decreases the level of in vitro infection, and protects susceptible mice. 4. Susceptible animals treated with anti-TGF-ß monoclonal antibodies change their immune response, not increasing the expression of IL-4 while increasing the expression of IFNÔ mRNA in their draining lymph nodes. Resistant animals treated with TGF-ß also change their pattern of immune response as indicated by an increase of the important Th2 cytokine IL-10 mRNA in the draining lymph node. 5. TGF-ß has profound effects on the host response to Leishmania in both mouse and man, and probably is an important parasite escape mechanism