RESUMO
Type I interferons (IFN-α and IFN-ß) are important for protection against many viral infections, whereas type II interferon (IFN-γ) is essential for host defense against some bacterial and parasitic pathogens. Study of IFN responses in human leprosy revealed an inverse correlation between IFN-ß and IFN-γ gene expression programs. IFN-γ and its downstream vitamin D-dependent antimicrobial genes were preferentially expressed in self-healing tuberculoid lesions and mediated antimicrobial activity against the pathogen Mycobacterium leprae in vitro. In contrast, IFN-ß and its downstream genes, including interleukin-10 (IL-10), were induced in monocytes by M. leprae in vitro and preferentially expressed in disseminated and progressive lepromatous lesions. The IFN-γ-induced macrophage vitamin D-dependent antimicrobial peptide response was inhibited by IFN-ß and by IL-10, suggesting that the differential production of IFNs contributes to protection versus pathogenesis in some human bacterial infections.
Assuntos
Interferon beta/imunologia , Interferon gama/imunologia , Hanseníase Virchowiana/imunologia , Hanseníase Tuberculoide/imunologia , Mycobacterium leprae/imunologia , 25-Hidroxivitamina D3 1-alfa-Hidroxilase/genética , 25-Hidroxivitamina D3 1-alfa-Hidroxilase/metabolismo , Peptídeos Catiônicos Antimicrobianos/genética , Peptídeos Catiônicos Antimicrobianos/metabolismo , Humanos , Interferon beta/genética , Interferon beta/metabolismo , Interferon gama/genética , Interferon gama/metabolismo , Interleucina-10/genética , Interleucina-10/metabolismo , Hanseníase Virchowiana/genética , Hanseníase Virchowiana/metabolismo , Hanseníase Tuberculoide/genética , Hanseníase Tuberculoide/metabolismo , Viabilidade Microbiana , Monócitos/imunologia , Monócitos/metabolismo , Mycobacterium leprae/fisiologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Calcitriol/genética , Receptores de Calcitriol/metabolismo , Transcriptoma , Tuberculose/genética , Tuberculose/imunologia , Regulação para Cima , beta-Defensinas/genética , beta-Defensinas/metabolismo , CatelicidinasRESUMO
We examined the effects of interferon beta (IFN-beta) on the production of liporabinomannan (LAM)-induced nitric oxide (NO) in peritoneal macrophages from low-responder and high-responder (C3H/HeJ and C3H/OuJ) mice. NO was produced in a dose response when induced by lipo-polysaccharide (LPS) or LAM plus interferon gamma (IFN-gamma) or IFN-beta in both high- and low-responder mice. In contrast to IFN-gamma, both high- and low-responder mice failed to induce nitrite production when IFN-beta was added, except at a high concentration of IFN-beta. Tau-Cl (0.5 mM) inhibited NO production about 50% in the high-responder strain when cells were activated with LPS or LAM in combination with either IFN-beta or IFN-gamma, and almost abolished NO production at 1.0 mM. In the low-responder strain, Tau-Cl (0.5 mM) significantly inhibited NO production when cells were activated with IFN-gamma or IFN-beta in addition to LPS or LAM, but did not completely inhibit NO production at 1.0 mM. Tau-Cl appears to play a potent role in regulating inflammatory reaction-induced bacterial or mycobacterial organisms. These data indicate a pivotal role for IFN-gamma and IFN-beta for the production of LPS and LAM initiated NO in peritoneal macrophages from low-responder (C3H/HeJ) mice.