Divergence of macrophage phagocytic and antimicrobial programs in leprosy.
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.
Montoya
Dennis
D
Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA.
Cruz
Daniel
D
Teles
Rosane M B
RM
Lee
Delphine J
DJ
Ochoa
Maria Teresa
MT
Krutzik
Stephan R
SR
Chun
Rene
R
Schenk
Mirjam
M
Zhang
Xiaoran
X
Ferguson
Benjamin G
BG
Burdick
Anne E
AE
Sarno
Euzenir N
EN
Rea
Thomas H
TH
Hewison
Martin
M
Adams
John S
JS
Cheng
Genhong
G
Modlin
Robert L
RL
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
D019409:Interleukin-15; D016753:Interleukin-10