title: Divergence of macrophage phagocytic and antimicrobial programs in leprosy.
abstract: Effective innate immunity against many microbial pathogens requires macrophage programs that upregulate phagocytosis and direct antimicrobial pathways, two functions generally assumed to be coordinately regulated. We investigated the regulation of these key functions in human blood-derived macrophages. Interleukin-10 (IL-10) induced the phagocytic pathway, including the C-type lectin CD209 and scavenger receptors, resulting in phagocytosis of mycobacteria and oxidized low-density lipoprotein. IL-15 induced the vitamin D-dependent antimicrobial pathway and CD209, yet the cells were less phagocytic. The differential regulation of macrophage functional programs was confirmed by analysis of leprosy lesions: the macrophage phagocytosis pathway was prominent in the clinically progressive, multibacillary form of the disease, whereas the vitamin D-dependent antimicrobial pathway predominated in the self-limited form and in patients undergoing reversal reactions from the multibacillary to the self-limited form. These data indicate that macrophage programs for phagocytosis and antimicrobial responses are distinct and differentially regulated in innate immunity to bacterial infections.
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Dennis
authors.initials: D
authors.lastname: Montoya
authors.forename: Daniel
authors.initials: D
authors.lastname: Cruz
authors.forename: Rosane M B
authors.initials: RM
authors.lastname: Teles
authors.forename: Delphine J
authors.initials: DJ
authors.lastname: Lee
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Ochoa
authors.forename: Stephan R
authors.initials: SR
authors.lastname: Krutzik
authors.forename: Rene
authors.initials: R
authors.lastname: Chun
authors.forename: Mirjam
authors.initials: M
authors.lastname: Schenk
authors.forename: Xiaoran
authors.initials: X
authors.lastname: Zhang
authors.forename: Benjamin G
authors.initials: BG
authors.lastname: Ferguson
authors.forename: Anne E
authors.initials: AE
authors.lastname: Burdick
authors.forename: Euzenir N
authors.initials: EN
authors.lastname: Sarno
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Rea
authors.forename: Martin
authors.initials: M
authors.lastname: Hewison
authors.forename: John S
authors.initials: JS
authors.lastname: Adams
authors.forename: Genhong
authors.initials: G
authors.lastname: Cheng
authors.forename: Robert L
authors.initials: RL
authors.lastname: Modlin
mesh_terms: D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology; D019409:Interleukin-15 / Q000276:immunology; D007918:Leprosy / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D050296:Microbial Viability; D009166:Mycobacterium leprae / Q000276:immunology* / Q000502:physiology*; D010587:Phagocytosis
chemical_list: D019409:Interleukin-15; D016753:Interleukin-10