Limited Contribution of IL-36 versus IL-1 and TNF Pathways in Host Response to Mycobacterial Infection

• Published in: PloS one Vol. 10; no. 5; p. e0126058
• Main Authors: Segueni, Noria, Vigne, Solenne, Palmer, Gaby, Bourigault, Marie-Laure, Olleros, Maria L, Vesin, Dominique, Garcia, Irene, Ryffel, Bernhard, Quesniaux, Valérie F J, Gabay, Cem
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 07.05.2015; Public Library of Science (PLoS)
• Subjects: Animal models; Animals; Bacillus Calmette-Guerin vaccine; Bacteria; BCG; Cytokines; Dendritic cells; Disease; Gene expression; Hospitals; Host-Pathogen Interactions; Immune response; Immune system; Immunology; Infections; Interleukin 1; Interleukin 1 receptors; Interleukin-1 - metabolism; Interleukins; Internal medicine; Lungs; Lymphocytes; Lymphocytes T; Medical schools; Medicine; Mice; Mice, Inbred C57BL; Mice, Knockout; Mycobacterium bovis; Mycobacterium infections; Mycobacterium Infections - metabolism; Mycobacterium tuberculosis; Pathology; Physiological aspects; Psoriasis; Rheumatology; Rodents; Signaling; Tuberculosis; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF; Tumor necrosis factor-α
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0126058

IL-36 cytokines are members of the IL-1 family of cytokines that stimulate dendritic cells and T cells leading to enhanced T helper 1 responses in vitro and in vivo; however, their role in host defense has not been fully addressed thus far. The objective of this study was to examine the role of IL-36R signaling in the control of mycobacterial infection, using models of systemic attenuated M. bovis BCG infection and virulent aerogenic M. tuberculosis infection. IL-36γ expression was increased in the lung of M. bovis BCG infected mice. However, IL-36R deficient mice infected with M. bovis BCG showed similar survival and control of the infection as compared to wild-type mice, although their lung pathology and CXCL1 response were transiently different. While highly susceptible TNF-α deficient mice succumbed with overwhelming M. tuberculosis infection, and IL-1RI deficient mice showed intermediate susceptibility, IL-36R-deficient mice controlled the infection, with bacterial burden, lung inflammation and pathology, similar to wild-type controls. Therefore, IL-36R signaling has only limited influence in the control of mycobacterial infection.