A POSSIBLE ROLE OF INSULIN-LIKE GROWTH FACTOR-I (IGF-I) ON THE FUNCTIONAL DEACTIVATION OF MACROPHAGES INFECTED WITH MYCOBACTERIA

Leonardo Ribeiro Batista Silva (Fio Cruz); Luciana Silva Rodrigues (Fio Cruz); Katherine Mattos Antunes (Fio Cruz); Maria Cristina Vidal Pessolani (Fio Cruz)

Mononuclear phagocytes are target cells for pathogenic mycobacteria such as Mycobacterium tuberculosis and Mycobacterium leprae. These bacteria are able to subvert macrophage microbicidal mechanisms and survive and replicate within these cells. However, the molecular mechanisms involved in this deactivation are not completely understood. Recently, we have reported that M. leprae induces the expression of insulin-like growth factor I (IGF-I) – an hormone with anti- apoptotic and proliferation activities– in human Schwann cells. Recently it has been reported that IGF-I can inhibit inducible nitric oxide synthase (iNOS) expression and consequently nitric oxide (NO) production in macrophages infected with Leishmania amazonensis. Based on these data, we have investigated the potential involvement of IGF-I on macrophage deactivation observed during mycobacterial infection. For this purpose, RAW 264.7 murine macrophages and primary human macrophages were treated or not with M. leprae and the expression of IGF-I was monitored by quantitative RT-PCR and specific sandwich ELISA. M. leprae treatment positively regulated the expression of RNAm for IGF-I and increased IGF-I protein levels in supernatants when compared with control cultures. Furthermore, we also investigated the effect of IGF-I on mycobacterium-induced iNOS expression and NO production in RAW 264.7 macrophages. NO production was evaluated by determination of nitrite concentration in the culture media using the Griess reagent and iNOS expression was monitored by Western Blot. IGF-I pre-treated cells showed a significant reduction in nitrite production after infection with mycobacteria that correlated with the downregulation of iNOS expression. These results suggest that IGF-I may contribute to mycobacterial persistent in the host by downmodulating host innate response during infection.