Treating patients infected with Mycobacterium tuberculosis is becoming increasingly difficult because of the emergence of multidrug-resistant bacteria. In Nature, Mayer-Barber et al. show that it is possible to enhance the host-mediated control of M. tuberculosis by changing the innate immune response to infection. The production of type I interferons (IFN-α and IFN-β) exacerbates infection with M. tuberculosis by inhibiting protective responses induced by signaling via IL-1. Conversely, IL-1 triggers the production of antimycobacterial cytokines and nitric oxide and inhibits the expression of IFN-α and IFN-β. IFN-α–IFN-β and IL-1 elicit competing pathways of eicosanoid metabolism that lead to the synthesis of lipoxin or prostaglandin E2 (PGE2), respectively. The administration of either IL-1 or PGE2 improves host control of infection with M. tuberculosis in mice. Retrospective analysis of cytokine profiles from patients with tuberculosis also shows that enhanced protection correlates with IL-1 and PGE2. Thus, it is possible to boost host control of M. tuberculosis by blocking the production of IFN-α and IFN-β and enhancing IL-1 responses.

Nature (25 June 2014) doi:10.1038/nature13489