Blocking IL-1α but not IL-1β increases susceptibility to chronic Mycobacterium tuberculosis infection in mice

IL-1 alpha and IL-1 beta are potent inflammatory cytokines and important mediators of immune responses to intracellular pathogens such as Mycobacterium tuberculosis (Mtb). Here, we investigated the role of IL-1 alpha and IL-1 beta during chronic Mtb infection and spontaneous reactivation in mice. For long-term neutralization of IL-1 alpha, IL-1 beta or both, mice were immunized with virus-like particles (VLPs) displaying either of the cytokines, inducing strong and long-lasting neutralizing IgG responses. Blocking of IL-1 alpha but not of IL-1 beta resulted in increased susceptibility to chronic infection with Mtb. Neutralizing either IL-1 alpha or IL-1 beta alone did not lead to increased reactivation of latent tuberculosis. The generation of antibodies neutralizing both IL-1 alpha and IL-1 beta simultaneously, did not influence weight gain during Mtb reactivation and the slight increase in pulmonary bacillary counts were not significant when compared to control-immunized group. Thus, the results suggest that IL-1a is the major mediator of the IL-1 RI-dependent and protective innate immune responses to Mtb in mice. Crown Copyright (C) 2010 Published by Elsevier Ltd. All rights reserved.