Cutting edge: in vivo induction of integrated HIV-1 expression by mycobacteria is critically dependent on Toll-like receptor 2.
Mycobacterial infection has been implicated as a possible factor in AIDS progression in populations where HIV-1 and Mycobacterium tuberculosis are coendemic. In support of this concept, we have previously shown that HIV-1-transgenic (Tg) mice infected with mycobacteria display enhanced viral gene and protein expression. In this study, we demonstrate that the induction of HIV-1 observed in this model is dependent on Toll-like receptor 2 (TLR2), a pattern recognition receptor known to be involved in mycobacteria-host interaction. Spleen cells from HIV-1-Tg mice deficient in TLR2 (Tg/TLR2(-/-)) were found to be completely defective in p24 production induced in response to live M. tuberculosis or Mycobacterium avium as well as certain mycobacterial products. Importantly, following in vivo mycobacterial infection, Tg/TLR2(-/-) mice failed to display the enhanced HIV-1 gag/env mRNA and p24 protein synthesis exhibited by wild-type Tg animals. Together, these results argue that TLR2 plays a crucial role in the activation of HIV-1 expression by mycobacterial coinfections.
Báfica
André
A
Immunobiology Section, National Institute of Allergy and Infectious Diseases and. Chemical Immunology Section, Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. abafica@niaid.nih.gov
Scanga
Charles A
CA
Schito
Marco L
ML
Hieny
Sara
S
Sher
Alan
A
D000818:Animals; D002473:Cell Wall / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D015967:Gene Expression Regulation, Viral / Q000276:immunology*; D016655:HIV Core Protein p24 / Q000096:biosynthesis / Q000235:genetics; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009162:Mycobacterium avium / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D013154:Spleen / Q000166:cytology / Q000382:microbiology / Q000821:virology; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D014376:Tuberculosis / Q000235:genetics / Q000276:immunology / Q000382:microbiology / Q000821:virology; D014775:Virus Activation / Q000235:genetics* / Q000276:immunology; D016662:Virus Integration / Q000235:genetics* / Q000276:immunology
D016655:HIV Core Protein p24; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors