title: Innate and adaptive interferons suppress IL-1α and IL-1β production by distinct pulmonary myeloid subsets during Mycobacterium tuberculosis infection.
abstract: Interleukin-1 (IL-1) receptor signaling is necessary for control of Mycobacterium tuberculosis (Mtb) infection, yet the role of its two ligands, IL-1α and IL-1β, and their regulation in vivo are poorly understood. Here, we showed that both IL-1α and IL-1β are critically required for host resistance and identified two multifunctional inflammatory monocyte-macrophage and DC populations that coexpressed both IL-1 species at the single-cell level in lungs of Mtb-infected mice. Moreover, we demonstrated that interferons (IFNs) played important roles in regulating IL-1 production by these cells in vivo. Type I interferons inhibited IL-1 production by both subsets whereas CD4(+) T cell-derived IFN-γ selectively suppressed monocyte-macrophages. These data provide a cellular basis for both the anti-inflammatory effects of IFNs and probacterial functions of type I IFNs during Mtb infection and reveal differential regulation of IL-1 production by distinct cell populations as an additional layer of complexity in the activity of IL-1 in vivo.
authors.affiliation: Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. mayerk@niaid.nih.gov
authors.forename: Katrin D
authors.initials: KD
authors.lastname: Mayer-Barber
authors.forename: Bruno B
authors.initials: BB
authors.lastname: Andrade
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Barber
authors.forename: Sara
authors.initials: S
authors.lastname: Hieny
authors.forename: Carl G
authors.initials: CG
authors.lastname: Feng
authors.forename: Patricia
authors.initials: P
authors.lastname: Caspar
authors.forename: Sandy
authors.initials: S
authors.lastname: Oland
authors.forename: Siamon
authors.initials: S
authors.lastname: Gordon
authors.forename: Alan
authors.initials: A
authors.lastname: Sher
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D007372:Interferons / Q000378:metabolism*; D053762:Interleukin-12 Subunit p40 / Q000096:biosynthesis; D053582:Interleukin-1alpha / Q000096:biosynthesis*; D053583:Interleukin-1beta / Q000096:biosynthesis*; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism; D010586:Phagocytes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D015398:Signal Transduction; D014397:Tuberculosis, Pulmonary / Q000276:immunology*
chemical_list: D000950:Antigens, Ly; D039481:CD11b Antigen; D053762:Interleukin-12 Subunit p40; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; C494192:Ly-6C antigen, mouse; D007372:Interferons