TY - JOUR
KW - 25-Hydroxyvitamin D3 1-alpha-Hydroxylase
KW - Antimicrobial Cationic Peptides
KW - Humans
KW - Interferon-beta
KW - Interferon-gamma
KW - Interleukin-10
KW - Leprosy, lepromatous
KW - Leprosy, Tuberculoid
KW - Microbial Viability
KW - Monocytes
KW - Mycobacterium leprae
KW - RNA, Messenger
KW - Receptors, Calcitriol
KW - Transcriptome
KW - Tuberculosis
KW - Up-Regulation
KW - Beta-Defensins
AU - Teles R
AU - Graeber T
AU - Krutzik SR
AU - Montoya DJ
AU - Schenk M
AU - Lee DJ
AU - Komisopoulou E
AU - Kelly-Scumpia K
AU - Chun R
AU - Iyer S
AU - Sarno E
AU - Rea T
AU - Hewison M
AU - Adams J
AU - Popper SJ
AU - Relman D
AU - Stenger S
AU - Bloom B
AU - Cheng G
AU - Modlin RL
AB - <p>Type I interferons (IFN-α and IFN-β) are important for protection against many viral infections, whereas type II interferon (IFN-γ) is essential for host defense against some bacterial and parasitic pathogens. Study of IFN responses in human leprosy revealed an inverse correlation between IFN-β and IFN-γ gene expression programs. IFN-γ and its downstream vitamin D-dependent antimicrobial genes were preferentially expressed in self-healing tuberculoid lesions and mediated antimicrobial activity against the pathogen Mycobacterium leprae in vitro. In contrast, IFN-β and its downstream genes, including interleukin-10 (IL-10), were induced in monocytes by M. leprae in vitro and preferentially expressed in disseminated and progressive lepromatous lesions. The IFN-γ-induced macrophage vitamin D-dependent antimicrobial peptide response was inhibited by IFN-β and by IL-10, suggesting that the differential production of IFNs contributes to protection versus pathogenesis in some human bacterial infections.</p>
BT - Science (New York, N.Y.)
C1 - http://www.ncbi.nlm.nih.gov/pubmed/23449998?dopt=Abstract
DA - 2013 Mar 22
DO - 10.1126/science.1233665
IS - 6126
J2 - Science
LA - eng
N2 - <p>Type I interferons (IFN-α and IFN-β) are important for protection against many viral infections, whereas type II interferon (IFN-γ) is essential for host defense against some bacterial and parasitic pathogens. Study of IFN responses in human leprosy revealed an inverse correlation between IFN-β and IFN-γ gene expression programs. IFN-γ and its downstream vitamin D-dependent antimicrobial genes were preferentially expressed in self-healing tuberculoid lesions and mediated antimicrobial activity against the pathogen Mycobacterium leprae in vitro. In contrast, IFN-β and its downstream genes, including interleukin-10 (IL-10), were induced in monocytes by M. leprae in vitro and preferentially expressed in disseminated and progressive lepromatous lesions. The IFN-γ-induced macrophage vitamin D-dependent antimicrobial peptide response was inhibited by IFN-β and by IL-10, suggesting that the differential production of IFNs contributes to protection versus pathogenesis in some human bacterial infections.</p>
PY - 2013
SP - 1448
EP - 53
T2 - Science (New York, N.Y.)
TI - Type I interferon suppresses type II interferon-triggered human anti-mycobacterial responses.
VL - 339
SN - 1095-9203
ER -