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-1β (IL-1β) produced in response to bacteria could impact viral reactivation. The transcription factors NF-κB 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.
Digital Object Identifier (DOI)
This study was supported by USPHS grant P20 RR020145 from the National Institute for Research Resources and funds from the University of Kentucky, College of Dentistry.
The title of this article was corrected in an Erratum, and that Erratum is attached to this record as Supplementary Content.
The original title of this article was ". . . Involves Toll-Like Receptor 4 and 9. . .". This record reflects the correct title.
Errata published in Clinical and Vaccine Immunology, v. 17, no. 11, p. 1825. DOI: http://dx.doi.org/10.1128/CVI.00424-10
Copyright © 2010, American Society for Microbiology. All Rights Reserved.
Gonzalez, Octavio A.; Li, Mengtao; Ebersole, Jeffrey L.; and Huang, Chifu B., "HIV-1 Reactivation Induced by the Periodontal Pathogens Fusobacterium nucleatum and Porphyromonas gingivalis Involves Toll-Like Receptor 2 and 9 Activation in Monocytes/Macrophages" (2010). Center for Oral Health Research Faculty Publications. 9.
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