title: Interdependence between Interleukin-1 and Tumor Necrosis Factor Regulates TNF-Dependent Control of Mycobacterium tuberculosis Infection.
abstract: The interleukin-1 receptor I (IL-1RI) is critical for host resistance to Mycobacterium tuberculosis (Mtb), yet the mechanisms of IL-1RI-mediated pathogen control remain unclear. Here, we show that without IL-1RI, Mtb-infected newly recruited Ly6G(hi) myeloid cells failed to upregulate tumor necrosis factor receptor I (TNF-RI) and to produce reactive oxygen species, resulting in compromised pathogen control. Furthermore, simultaneous ablation of IL-1RI and TNF-RI signaling on either stroma or hematopoietic cells led to early lethality, indicating non-redundant and synergistic roles of IL-1 and TNF in mediating macrophage-stroma cross-talk that was critical for optimal control of Mtb infection. Finally, we show that even in the presence of functional Mtb-specific adaptive immunity, the lack of IL-1α and not IL-1β led to an exuberant intracellular pathogen replication and progressive non-resolving inflammation. Our study reveals functional interdependence between IL-1 and TNF in enabling Mtb control mechanisms that are critical for host survival.
authors.affiliation: Lowance Center for Human Immunology, Emory University, Atlanta, GA 30322, USA. Electronic address: ncdipaolo@emory.edu.
authors.forename: Nelson C
authors.initials: NC
authors.lastname: Di Paolo
authors.affiliation: Center for Infectious Disease Research (formerly Seattle Biomedical Research Institute), Seattle, WA 98109, USA.
authors.forename: Shahin
authors.initials: S
authors.lastname: Shafiani
authors.affiliation: Center for Infectious Disease Research (formerly Seattle Biomedical Research Institute), Seattle, WA 98109, USA.
authors.forename: Tracey
authors.initials: T
authors.lastname: Day
authors.forename: Thalia
authors.initials: T
authors.lastname: Papayannopoulou
authors.affiliation: Division of Hematology, Department of Medicine, University of Washington, Seattle, WA 98195, USA.
authors.forename: Thalia
authors.initials: T
authors.lastname: Papayannoupoulou
authors.affiliation: Division of Hematology, Department of Medicine, University of Washington, Seattle, WA 98195, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Russell
authors.affiliation: Laboratory of Molecular Pathogenesis, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.affiliation: Center for Infectious Disease Research (formerly Seattle Biomedical Research Institute), Seattle, WA 98109, USA.
authors.forename: David
authors.initials: D
authors.lastname: Sherman
authors.affiliation: Center for Infectious Disease Research (formerly Seattle Biomedical Research Institute), Seattle, WA 98109, USA; Department of Immunology, University of Washington, Seattle, WA 98195, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Urdahl
authors.affiliation: Lowance Center for Human Immunology, Emory University, Atlanta, GA 30322, USA; Center for Transplantation and Immuno-mediated Disorders, Emory University, Atlanta, GA 30322, USA; Emory Vaccine Center and Departments of Pediatrics and Medicine, Emory University, Atlanta, GA 30322, USA. Electronic address: dmitryshay@emory.edu.
authors.forename: Dmitry M
authors.initials: DM
authors.lastname: Shayakhmetov
mesh_terms: D000818:Animals; D002469:Cell Separation; D004195:Disease Models, Animal; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D053582:Interleukin-1alpha / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis; D053573:Receptors, Interleukin-1 Type I / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
chemical_list: C583355:IL1R1 protein, mouse; D053582:Interleukin-1alpha; D053573:Receptors, Interleukin-1 Type I; D014409:Tumor Necrosis Factor-alpha