Interleukin-1 signaling ts essential for host defense during murine pulmonary tuberculosis

Interleukin (IL)-1 signaling is required for the containment of infections with intracellular microorganisms, such as Listeria monocytogenes and Leish mania major. To determine the role of IL-1 in the host response to tubercul osis, we infected IL-1 type I receptor-deficient (IL-1R(-/-)) mice, in whic h IL-1 does not exert effects, with Mycobacterium tuberculosis. IL-1R(-/-) mice were more susceptible to pulmonary tuberculosis, as reflected by an in creased mortality and an enhanced mycobacterial outgrowth in lungs and dist ant organs, which was associated with defective granuloma formation, contai ning fewer macrophages and fewer lymphocytes, whereas granulocytes were abu ndant. Lymphocytes were predominantly confined to perivascular areas, sugge sting a defective migration of cells into inflamed tissue in the absence of IL-1 signaling. Impaired host defense in IL-1R(-/-) mice was further chara cterized by a decrease in the ability of splenocytes to produce interferon- gamma, Analysis of these data suggests that IL-1 plays an important role in the immune response to M. tuberculosis.