title: Blocking IL-1α but not IL-1β increases susceptibility to chronic Mycobacterium tuberculosis infection in mice.
abstract: IL-1α and IL-1β 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-1α and IL-1β during chronic Mtb infection and spontaneous reactivation in mice. For long-term neutralization of IL-1α, IL-1β 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-1α but not of IL-1β resulted in increased susceptibility to chronic infection with Mtb. Neutralizing either IL-1α or IL-1β alone did not lead to increased reactivation of latent tuberculosis. The generation of antibodies neutralizing both IL-1α and IL-1β 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-1α is the major mediator of the IL-1RI-dependent and protective innate immune responses to Mtb in mice.
authors.affiliation: International Centre for Genetic Engineering and Biotechnology, University of Cape Town, Cape Town 7925, South Africa.
authors.forename: Reto
authors.initials: R
authors.lastname: Guler
authors.forename: Suraj P
authors.initials: SP
authors.lastname: Parihar
authors.forename: Gunther
authors.initials: G
authors.lastname: Spohn
authors.forename: Pål
authors.initials: P
authors.lastname: Johansen
authors.forename: Frank
authors.initials: F
authors.lastname: Brombacher
authors.forename: Martin F
authors.initials: MF
authors.lastname: Bachmann
mesh_terms: D000818:Animals; D004198:Disease Susceptibility; D005260:Female; D006801:Humans; D053582:Interleukin-1alpha / Q000037:antagonists & inhibitors / Q000276:immunology*; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000472:pathogenicity; D014376:Tuberculosis / Q000276:immunology* / Q000382:microbiology
chemical_list: D053582:Interleukin-1alpha; D053583:Interleukin-1beta