title: IL12B expression is sustained by a heterogenous population of myeloid lineages during tuberculosis.
abstract: IL12B is required for resistance to Mycobacterium tuberculosis (Mtb) infection, promoting the initiation and maintenance of Mtb-specific effector responses. While this makes the IL12-pathway an attractive target for experimental tuberculosis (TB) therapies, data regarding what lineages express IL12B after infection is established are limited. This is not obvious in the lung, an organ in which both hematopoietic and non-hematopoietic lineages produce IL12p40 upon pathogen encounter. Here, we use radiation bone marrow chimeras and Yet40 reporter mice to determine what lineages produce IL12p40 during experimental TB. We observed that hematopoietic IL12p40-production was sufficient to control Mtb, with no contribution by non-hematopoietic lineages. Furthermore, rather than being produced by a single subset, IL12p40 was produced by cells that were heterogenous in their size, granularity, autofluorescence and expression of CD11c, CD11b and CD8α. While depending on the timepoint and tissue examined, the surface phenotype of IL12p40-producers most closely resembled macrophages based on previous surveys of lung myeloid lineages. Importantly, depletion of CD11c(hi) cells during infection had no affect on lung IL12p40-concentrations. Collectively, our data demonstrate that IL12p40 production is sustained by a heterogenous population of myeloid lineages during experimental TB, and that redundant mechanisms of IL12p40-production exist when CD11c(hi) lineages are absent.
authors.affiliation: Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, WI 53226, USA. areeme@mcw.edu
authors.forename: Allison E
authors.initials: AE
authors.lastname: Reeme
authors.forename: Halli E
authors.initials: HE
authors.lastname: Miller
authors.forename: Richard T
authors.initials: RT
authors.lastname: Robinson
mesh_terms: D000818:Animals; D058491:Bacterial Load; D001854:Bone Marrow Cells / Q000276:immunology*; D039521:CD11c Antigen / Q000032:analysis; D007113:Immunity, Innate; D053762:Interleukin-12 Subunit p40 / Q000096:biosynthesis* / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000382:microbiology; D008198:Lymph Nodes / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000302:isolation & purification; D011828:Radiation Chimera / Q000276:immunology; D013154:Spleen / Q000276:immunology / Q000382:microbiology; D014376:Tuberculosis / Q000276:immunology* / Q000382:microbiology
chemical_list: D039521:CD11c Antigen; D053762:Interleukin-12 Subunit p40