title: Vitamin D is required for IFN-gamma-mediated antimicrobial activity of human macrophages.
abstract: Control of tuberculosis worldwide depends on our understanding of human immune mechanisms, which combat the infection. Acquired T cell responses are critical for host defense against microbial pathogens, yet the mechanisms by which they act in humans remain unclear. We report that T cells, by the release of interferon-γ (IFN-γ), induce autophagy, phagosomal maturation, the production of antimicrobial peptides such as cathelicidin, and antimicrobial activity against Mycobacterium tuberculosis in human macrophages via a vitamin D-dependent pathway. IFN-γ induced the antimicrobial pathway in human macrophages cultured in vitamin D-sufficient sera, but not in sera from African-Americans that have lower amounts of vitamin D and who are more susceptible to tuberculosis. In vitro supplementation of vitamin D-deficient serum with 25-hydroxyvitamin D3 restored IFN-γ-induced antimicrobial peptide expression, autophagy, phagosome-lysosome fusion, and antimicrobial activity. These results suggest a mechanism in which vitamin D is required for acquired immunity to overcome the ability of intracellular pathogens to evade macrophage-mediated antimicrobial responses. The present findings underscore the importance of adequate amounts of vitamin D in all human populations for sustaining both innate and acquired immunity against infection.
authors: Division of Dermatology, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA.
authors: Mario
authors: M
authors: Fabri
authors: Steffen
authors: S
authors: Stenger
authors: Dong-Min
authors: DM
authors: Shin
authors: Jae-Min
authors: JM
authors: Yuk
authors: Philip T
authors: PT
authors: Liu
authors: Susan
authors: S
authors: Realegeno
authors: Hye-Mi
authors: HM
authors: Lee
authors: Stephan R
authors: SR
authors: Krutzik
authors: Mirjam
authors: M
authors: Schenk
authors: Peter A
authors: PA
authors: Sieling
authors: Rosane
authors: R
authors: Teles
authors: Dennis
authors: D
authors: Montoya
authors: Shankar S
authors: SS
authors: Iyer
authors: Heiko
authors: H
authors: Bruns
authors: David M
authors: DM
authors: Lewinsohn
authors: Bruce W
authors: BW
authors: Hollis
authors: Martin
authors: M
authors: Hewison
authors: John S
authors: JS
authors: Adams
authors: Andreas
authors: A
authors: Steinmeyer
authors: Ulrich
authors: U
authors: Zügel
authors: Genhong
authors: G
authors: Cheng
authors: Eun-Kyeong
authors: EK
authors: Jo
authors: Barry R
authors: BR
authors: Bloom
authors: Robert L
authors: RL
authors: Modlin
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry; D001343:Autophagy; D002112:Calcifediol / Q000097:blood; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D008213:Lymphocyte Activation; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008954:Models, Biological; D009000:Monocytes / Q000166:cytology; D009169:Mycobacterium tuberculosis / Q000378:metabolism; D014376:Tuberculosis / Q000382:microbiology; D014807:Vitamin D / Q000378:metabolism*
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D014807:Vitamin D; D007371:Interferon-gamma; D002112:Calcifediol