Most individuals infected with mycobacteria can clear or contain these intracellular parasites, but others may develop disseminated infections. In Science, Modlin and colleagues show that the control of mycobacterial infections is dictated by the type of interferon (IFN) produced. Patients with self-healing tuberculoid leprosy, caused by Mycobacterium leprae, express more IFN-γ, leading to the upregulation of vitamin D–dependent antimicrobial peptides, such as cathelicidin and β-defensin 2. In contrast, patients with disseminated lepromatous leprosy express more IFN-β and show increased expression of IFN-β–dependent genes, including more IL-10. Blocking IL-10 reduces the bacterial load in infected human monocytes. Analysis of published tuberculosis gene expression profiles reveals a similar dichotomy of IFN-γ– and IFN-β–mediated responses in resolving as opposed to chronic forms of the disease. These findings could be used to combat chronic mycobacterial infection by modulating IFN-β and IL-10.

Science 339, 1448–1453 (2013)