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Type I Interferon Suppresses Type II Interferon–Triggered Human Anti-Mycobacterial Responses

Science  22 Mar 2013:
Vol. 339, Issue 6126, pp. 1448-1453
DOI: 10.1126/science.1233665

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Interfering with Interferons

Infections with Mycobacteria, including Mycobacterium leprae or M. tuberculosis, vary substantially in their clinical presentation. For instance, in some cases of M. leprae, the infection is self-healing with very few lesions. In contrast, some people experience the disseminated form, where skin lesions abound and bacteria are abundant. In patients infected with M. leprae, Teles et al. (p. 1448, published online 28 February) found that the disseminated disease associates with a type I interferon gene signature, whereas the self-healing form associates with a type II interferon gene signature. In cultured cells, type I interferon and its downstream signaling cascade inhibited the antimicrobial response induced by type II interferons, providing a potential explanation for why robust disease rather than protection is seen in some cases of infection.

Abstract

Type I interferons (IFN-α and IFN-β) 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-β 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-β 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-β and by IL-10, suggesting that the differential production of IFNs contributes to protection versus pathogenesis in some human bacterial infections.

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