HIV-1 reactivation induced by the periodontal pathogens Fusobacterium nucleatum and Porphyromonas gingivalis involves Toll-like receptor 2 [corrected] and 9 activation in monocytes/macrophages.
Although oral coinfections (e.g., periodontal disease) are highly prevalent in human immunodeficiency virus type 1-positive (HIV-1(+)) patients and appear to positively correlate with viral load levels, the potential for oral bacteria to induce HIV-1 reactivation in latently infected cells has received little attention. We showed that HIV-1 long terminal repeat (LTR) promoter activation can be induced by periodontopathogens in monocytes/macrophages; nevertheless, the mechanisms involved in this response remain undetermined. Since Toll-like receptor 2 (TLR2), TLR4, and TLR9 activation have been involved in HIV-1 recrudescence, we sought to determine the role of these TLRs in HIV-1 reactivation induced by the periodontal pathogens Fusobacterium nucleatum and Porphyromonas gingivalis using BF24 monocytes/macrophages stably transfected with the HIV-1 promoter driving chloramphenicol acetyltransferase (CAT) expression and THP89GFP cells, a model of HIV-1 latency. We demonstrated that TLR9 activation by F. nucleatum and TLR2 activation by both bacteria appear to be involved in HIV-1 reactivation; however, TLR4 activation had no effect. Moreover, the autocrine activity of tumor necrosis factor alpha (TNF-alpha) but not interleukin-1beta (IL-1beta) produced in response to bacteria could impact viral reactivation. The transcription factors NF-kappaB and Sp1 appear to be positively regulating HIV-1 reactivation induced by these oral pathogens. These results suggest that oral Gram-negative bacteria (F. nucleatum and P. gingivalis) associated with oral and systemic chronic inflammatory disorders enhance HIV-1 reactivation in monocytes/macrophages through TLR2 and TLR9 activation in a mechanism that appears to be transcriptionally regulated. Increased bacterial growth and emergence of these bacteria or their products accompanying chronic oral inflammatory diseases could be risk modifiers for viral replication, systemic immune activation, and AIDS progression in HIV-1(+) patients.
González
Octavio A
OA
Center for Oral Health Research, College of Dentistry, University of Kentucky, Lexington, KY 40536-0305, USA.
Li
Mengtao
M
Ebersole
Jeffrey L
JL
Huang
Chifu B
CB
D002460:Cell Line; D016967:Fusobacterium nucleatum / Q000276:immunology* / Q000472:pathogenicity; D015497:HIV-1 / Q000276:immunology / Q000472:pathogenicity*; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D009000:Monocytes / Q000276:immunology / Q000821:virology*; D016328:NF-kappa B / Q000378:metabolism; D016966:Porphyromonas gingivalis / Q000276:immunology* / Q000472:pathogenicity; D016329:Sp1 Transcription Factor / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014775:Virus Activation
D053583:Interleukin-1beta; D016328:NF-kappa B; D016329:Sp1 Transcription Factor; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9; D014409:Tumor Necrosis Factor-alpha