Gonococcal lipooligosaccharide suppresses HIV infection in human primary macrophages through induction of innate immunity.
Gonorrhea often occurs as a coinfection with human immunodeficiency virus (HIV). Lipooligosaccharide (LOS) is a component of the gonococcal outer membrane that induces innate immunity through engagement of Toll-like receptor 4 (TLR4). We investigated the effects that LOS from 5 different strains of Neisseria gonorrhoeae have on HIV infection and on HIV provirus in primary human macrophages. LOS-treated human primary macrophages developed resistance to new HIV infection as well as to HIV provirus. Gonococcal LOS from the 5 strains and lipopolysaccharide (LPS) from Escherichia coli showed no significant difference in their anti-HIV activities. Suppression of HIV provirus resulted from the induction of interferon (IFN)-beta and subsequent activation of signal transducer and activator of transcription 1. Neutralization of IFN-beta , but not IFN-alpha , via antibody significantly reduced the anti-HIV activity induced by LOS and LPS. We conclude that LOS expressed by various strains of N. gonorrhoeae induce specific innate immune responses through TLR4 signaling, resulting in anti-HIV activity in human primary macrophages in vitro.
Liu
Xinyan
X
Division of Infectious Diseases, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA. xinyan.liu@mssm.edu
Mosoian
Arevik
A
Li-Yun Chang
Theresa
T
Zerhouni-Layachi
Bouchra
B
Snyder
Alexandra
A
Jarvis
Gary A
GA
Klotman
Mary E
ME
D006069:Gonorrhea / Q000150:complications; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy / Q000276:immunology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D016899:Interferon-beta / Q000187:drug effects / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D009344:Neisseria gonorrhoeae; D011533:Proviruses / Q000187:drug effects; D050794:STAT1 Transcription Factor / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D014779:Virus Replication / Q000187:drug effects
D008070:Lipopolysaccharides; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; C023023:lipid-linked oligosaccharides; D016899:Interferon-beta