title: Annexin1 regulates DC efferocytosis and cross-presentation during Mycobacterium tuberculosis infection.
abstract: The phagocytosis of apoptotic cells and associated vesicles (efferocytosis) by DCs is an important mechanism for both self tolerance and host defense. Although some of the engulfment ligands involved in efferocytosis have been identified and studied in vitro, the contributions of these ligands in vivo remain ill defined. Here, we determined that during Mycobacterium tuberculosis (Mtb) infection, the engulfment ligand annexin1 is an important mediator in DC cross-presentation that increases efferocytosis in DCs and intrinsically enhances the capacity of the DC antigen-presenting machinery. Annexin1-deficient mice were highly susceptible to Mtb infection and showed an impaired Mtb antigen-specific CD8+ T cell response. Importantly, annexin1 expression was greatly downregulated in Mtb-infected human blood monocyte-derived DCs, indicating that reduction of annexin1 is a critical mechanism for immune evasion by Mtb. Collectively, these data indicate that annexin1 is essential in immunity to Mtb infection and mediates the power of DC efferocytosis and cross-presentation.
authors.forename: Fanny
authors.initials: F
authors.lastname: Tzelepis
authors.forename: Mark
authors.initials: M
authors.lastname: Verway
authors.forename: Jamal
authors.initials: J
authors.lastname: Daoud
authors.forename: Joshua
authors.initials: J
authors.lastname: Gillard
authors.forename: Kimya
authors.initials: K
authors.lastname: Hassani-Ardakani
authors.forename: Jonathan
authors.initials: J
authors.lastname: Dunn
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Downey
authors.forename: Marilena Elena
authors.initials: ME
authors.lastname: Gentile
authors.forename: Joanna
authors.initials: J
authors.lastname: Jaworska
authors.forename: Anthony Michel Jean
authors.initials: AM
authors.lastname: Sanchez
authors.forename: Yohann
authors.initials: Y
authors.lastname: Nédélec
authors.forename: Hojatollah
authors.initials: H
authors.lastname: Vali
authors.forename: Maryam
authors.initials: M
authors.lastname: Tabrizian
authors.forename: Arnold Scott
authors.initials: AS
authors.lastname: Kristof
authors.forename: Irah Luther
authors.initials: IL
authors.lastname: King
authors.forename: Luis Bruno
authors.initials: LB
authors.lastname: Barreiro
authors.forename: Maziar
authors.initials: M
authors.lastname: Divangahi
mesh_terms: D000818:Animals; D017305:Annexin A1 / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D045142:Cross-Priming; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007111:Immunity, Cellular; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology / Q000473:pathology; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010587:Phagocytosis; D014376:Tuberculosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology
chemical_list: D017305:Annexin A1