title: Limited Contribution of IL-36 versus IL-1 and TNF Pathways in Host Response to Mycobacterial Infection.
abstract: 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.
authors.affiliation: CNRS, UMR7355, Orleans, France; University of Orleans, Experimental and Molecular Immunology and Neurogenetics, Orleans, France.
authors.forename: Noria
authors.initials: N
authors.lastname: Segueni
authors.affiliation: Division of Rheumatology, Department of Internal Medicine Specialties, University Hospitals of Geneva, Geneva, Switzerland; Department of Pathology and Immunology, University of Geneva Medical School, Geneva, Switzerland.
authors.forename: Solenne
authors.initials: S
authors.lastname: Vigne
authors.affiliation: Division of Rheumatology, Department of Internal Medicine Specialties, University Hospitals of Geneva, Geneva, Switzerland; Department of Pathology and Immunology, University of Geneva Medical School, Geneva, Switzerland.
authors.forename: Gaby
authors.initials: G
authors.lastname: Palmer
authors.affiliation: CNRS, UMR7355, Orleans, France; University of Orleans, Experimental and Molecular Immunology and Neurogenetics, Orleans, France.
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Bourigault
authors.affiliation: Department of Pathology and Immunology, University of Geneva Medical School, Geneva, Switzerland.
authors.forename: Maria L
authors.initials: ML
authors.lastname: Olleros
authors.affiliation: Department of Pathology and Immunology, University of Geneva Medical School, Geneva, Switzerland.
authors.forename: Dominique
authors.initials: D
authors.lastname: Vesin
authors.affiliation: Department of Pathology and Immunology, University of Geneva Medical School, Geneva, Switzerland.
authors.forename: Irene
authors.initials: I
authors.lastname: Garcia
authors.affiliation: CNRS, UMR7355, Orleans, France; University of Orleans, Experimental and Molecular Immunology and Neurogenetics, Orleans, France; Division of Immunology, Institute of Infectious Disease and Molecular Medicine, Health Sciences Faculty, University of Cape Town, Cape Town, South Africa.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Ryffel
authors.affiliation: CNRS, UMR7355, Orleans, France; University of Orleans, Experimental and Molecular Immunology and Neurogenetics, Orleans, France.
authors.forename: Valérie F J
authors.initials: VF
authors.lastname: Quesniaux
authors.affiliation: Division of Rheumatology, Department of Internal Medicine Specialties, University Hospitals of Geneva, Geneva, Switzerland; Department of Pathology and Immunology, University of Geneva Medical School, Geneva, Switzerland.
authors.forename: Cem
authors.initials: C
authors.lastname: Gabay
mesh_terms: D000818:Animals; D054884:Host-Pathogen Interactions; D007375:Interleukin-1 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009164:Mycobacterium Infections / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; C000606572:interleukin-36, mouse