Contrasting roles for TLR ligands in HIV-1 pathogenesis

Beda Brichacek, Christophe Vanpouille, Yana Kiselyeva, Angelique Biancotto, Melanie Merbah, Ivan Hirsch, Andrea Lisco, Jean-Charles B. Grivel, Leonid Margolis

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

The first line of a host's response to various pathogens is triggered by their engagement of cellular pattern recognition receptors (PRRs). Binding of microbial ligands to these receptors leads to the induction of a variety of cellular factors that alter intracellular and extracellular environment and interfere directly or indirectly with the life cycle of the triggering pathogen. Such changes may also affect any coinfecting microbe. Using ligands to Toll-like receptors (TLRs) 5 and 9, we examined their effect on human immunodeficiency virus (HIV)-1 replication in lymphoid tissue ex vivo. We found marked differences in the outcomes of such treatment. While flagellin (TLR5 agonist) treatment enhanced replication of CC chemokine receptor 5 (CCR 5)-tropic and CXC chemokine receptor 4 (CXCR4)-tropic HIV-1, treatment with oligodeoxynucleotide (ODN) M362 (TLR9 agonist) suppressed both viral variants. The differential effects of these TLR ligands on HIV-1 replication correlated with changes in production of CC chemokines CCL3, CCL4, CCL5, and of CXC chemokines CXCL10, and CXCL12 in the ligand-treated HIV-1-infected tissues. The nature and/or magnitude of these changes were dependent on the ligand as well as on the HIV-1 viral strain. Moreover, the tested ligands differed in their ability to induce cellular activation as evaluated by the expression of the cluster of differentiation markers (CD) 25, CD38, CD39, CD69, CD154, and human leukocyte antigen D related (HLA)-DR as well as of a cell proliferation marker, Ki67, and of CCR5. No significant effect of the ligand treatment was observed on apoptosis and cell death/loss in the treated lymphoid tissue ex vivo. Our results suggest that binding of microbial ligands to TLRs is one of the mechanisms that mediate interactions between coinfected microbes and HIV-1 in human tissues. Thus, the engagement of appropriate TLRs by microbial molecules or their mimetic might become a new strategy for HIV therapy or prevention.

Original languageEnglish
Article numbere12831
Pages (from-to)1-12
Number of pages12
JournalPLoS One
Volume5
Issue number9
DOIs
Publication statusPublished - 2010
Externally publishedYes

Fingerprint

Toll-Like Receptors
Human immunodeficiency virus 1
Viruses
HIV-1
pathogenesis
Ligands
Tissue
Tropics
Lymphoid Tissue
Pathogens
Virus Replication
agonists
tropics
Toll-Like Receptor 5
CD Antigens
CCR5 Receptors
Toll-Like Receptor 9
Chemokine CCL4
Chemokine CXCL10
CXCR4 Receptors

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Brichacek, B., Vanpouille, C., Kiselyeva, Y., Biancotto, A., Merbah, M., Hirsch, I., ... Margolis, L. (2010). Contrasting roles for TLR ligands in HIV-1 pathogenesis. PLoS One, 5(9), 1-12. [e12831]. https://doi.org/10.1371/journal.pone.0012831

Contrasting roles for TLR ligands in HIV-1 pathogenesis. / Brichacek, Beda; Vanpouille, Christophe; Kiselyeva, Yana; Biancotto, Angelique; Merbah, Melanie; Hirsch, Ivan; Lisco, Andrea; Grivel, Jean-Charles B.; Margolis, Leonid.

In: PLoS One, Vol. 5, No. 9, e12831, 2010, p. 1-12.

Research output: Contribution to journalArticle

Brichacek, B, Vanpouille, C, Kiselyeva, Y, Biancotto, A, Merbah, M, Hirsch, I, Lisco, A, Grivel, J-CB & Margolis, L 2010, 'Contrasting roles for TLR ligands in HIV-1 pathogenesis', PLoS One, vol. 5, no. 9, e12831, pp. 1-12. https://doi.org/10.1371/journal.pone.0012831
Brichacek B, Vanpouille C, Kiselyeva Y, Biancotto A, Merbah M, Hirsch I et al. Contrasting roles for TLR ligands in HIV-1 pathogenesis. PLoS One. 2010;5(9):1-12. e12831. https://doi.org/10.1371/journal.pone.0012831
Brichacek, Beda ; Vanpouille, Christophe ; Kiselyeva, Yana ; Biancotto, Angelique ; Merbah, Melanie ; Hirsch, Ivan ; Lisco, Andrea ; Grivel, Jean-Charles B. ; Margolis, Leonid. / Contrasting roles for TLR ligands in HIV-1 pathogenesis. In: PLoS One. 2010 ; Vol. 5, No. 9. pp. 1-12.
@article{759b539990d14057ad35cfe75dbe8f87,
title = "Contrasting roles for TLR ligands in HIV-1 pathogenesis",
abstract = "The first line of a host's response to various pathogens is triggered by their engagement of cellular pattern recognition receptors (PRRs). Binding of microbial ligands to these receptors leads to the induction of a variety of cellular factors that alter intracellular and extracellular environment and interfere directly or indirectly with the life cycle of the triggering pathogen. Such changes may also affect any coinfecting microbe. Using ligands to Toll-like receptors (TLRs) 5 and 9, we examined their effect on human immunodeficiency virus (HIV)-1 replication in lymphoid tissue ex vivo. We found marked differences in the outcomes of such treatment. While flagellin (TLR5 agonist) treatment enhanced replication of CC chemokine receptor 5 (CCR 5)-tropic and CXC chemokine receptor 4 (CXCR4)-tropic HIV-1, treatment with oligodeoxynucleotide (ODN) M362 (TLR9 agonist) suppressed both viral variants. The differential effects of these TLR ligands on HIV-1 replication correlated with changes in production of CC chemokines CCL3, CCL4, CCL5, and of CXC chemokines CXCL10, and CXCL12 in the ligand-treated HIV-1-infected tissues. The nature and/or magnitude of these changes were dependent on the ligand as well as on the HIV-1 viral strain. Moreover, the tested ligands differed in their ability to induce cellular activation as evaluated by the expression of the cluster of differentiation markers (CD) 25, CD38, CD39, CD69, CD154, and human leukocyte antigen D related (HLA)-DR as well as of a cell proliferation marker, Ki67, and of CCR5. No significant effect of the ligand treatment was observed on apoptosis and cell death/loss in the treated lymphoid tissue ex vivo. Our results suggest that binding of microbial ligands to TLRs is one of the mechanisms that mediate interactions between coinfected microbes and HIV-1 in human tissues. Thus, the engagement of appropriate TLRs by microbial molecules or their mimetic might become a new strategy for HIV therapy or prevention.",
author = "Beda Brichacek and Christophe Vanpouille and Yana Kiselyeva and Angelique Biancotto and Melanie Merbah and Ivan Hirsch and Andrea Lisco and Grivel, {Jean-Charles B.} and Leonid Margolis",
year = "2010",
doi = "10.1371/journal.pone.0012831",
language = "English",
volume = "5",
pages = "1--12",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "9",

}

TY - JOUR

T1 - Contrasting roles for TLR ligands in HIV-1 pathogenesis

AU - Brichacek, Beda

AU - Vanpouille, Christophe

AU - Kiselyeva, Yana

AU - Biancotto, Angelique

AU - Merbah, Melanie

AU - Hirsch, Ivan

AU - Lisco, Andrea

AU - Grivel, Jean-Charles B.

AU - Margolis, Leonid

PY - 2010

Y1 - 2010

N2 - The first line of a host's response to various pathogens is triggered by their engagement of cellular pattern recognition receptors (PRRs). Binding of microbial ligands to these receptors leads to the induction of a variety of cellular factors that alter intracellular and extracellular environment and interfere directly or indirectly with the life cycle of the triggering pathogen. Such changes may also affect any coinfecting microbe. Using ligands to Toll-like receptors (TLRs) 5 and 9, we examined their effect on human immunodeficiency virus (HIV)-1 replication in lymphoid tissue ex vivo. We found marked differences in the outcomes of such treatment. While flagellin (TLR5 agonist) treatment enhanced replication of CC chemokine receptor 5 (CCR 5)-tropic and CXC chemokine receptor 4 (CXCR4)-tropic HIV-1, treatment with oligodeoxynucleotide (ODN) M362 (TLR9 agonist) suppressed both viral variants. The differential effects of these TLR ligands on HIV-1 replication correlated with changes in production of CC chemokines CCL3, CCL4, CCL5, and of CXC chemokines CXCL10, and CXCL12 in the ligand-treated HIV-1-infected tissues. The nature and/or magnitude of these changes were dependent on the ligand as well as on the HIV-1 viral strain. Moreover, the tested ligands differed in their ability to induce cellular activation as evaluated by the expression of the cluster of differentiation markers (CD) 25, CD38, CD39, CD69, CD154, and human leukocyte antigen D related (HLA)-DR as well as of a cell proliferation marker, Ki67, and of CCR5. No significant effect of the ligand treatment was observed on apoptosis and cell death/loss in the treated lymphoid tissue ex vivo. Our results suggest that binding of microbial ligands to TLRs is one of the mechanisms that mediate interactions between coinfected microbes and HIV-1 in human tissues. Thus, the engagement of appropriate TLRs by microbial molecules or their mimetic might become a new strategy for HIV therapy or prevention.

AB - The first line of a host's response to various pathogens is triggered by their engagement of cellular pattern recognition receptors (PRRs). Binding of microbial ligands to these receptors leads to the induction of a variety of cellular factors that alter intracellular and extracellular environment and interfere directly or indirectly with the life cycle of the triggering pathogen. Such changes may also affect any coinfecting microbe. Using ligands to Toll-like receptors (TLRs) 5 and 9, we examined their effect on human immunodeficiency virus (HIV)-1 replication in lymphoid tissue ex vivo. We found marked differences in the outcomes of such treatment. While flagellin (TLR5 agonist) treatment enhanced replication of CC chemokine receptor 5 (CCR 5)-tropic and CXC chemokine receptor 4 (CXCR4)-tropic HIV-1, treatment with oligodeoxynucleotide (ODN) M362 (TLR9 agonist) suppressed both viral variants. The differential effects of these TLR ligands on HIV-1 replication correlated with changes in production of CC chemokines CCL3, CCL4, CCL5, and of CXC chemokines CXCL10, and CXCL12 in the ligand-treated HIV-1-infected tissues. The nature and/or magnitude of these changes were dependent on the ligand as well as on the HIV-1 viral strain. Moreover, the tested ligands differed in their ability to induce cellular activation as evaluated by the expression of the cluster of differentiation markers (CD) 25, CD38, CD39, CD69, CD154, and human leukocyte antigen D related (HLA)-DR as well as of a cell proliferation marker, Ki67, and of CCR5. No significant effect of the ligand treatment was observed on apoptosis and cell death/loss in the treated lymphoid tissue ex vivo. Our results suggest that binding of microbial ligands to TLRs is one of the mechanisms that mediate interactions between coinfected microbes and HIV-1 in human tissues. Thus, the engagement of appropriate TLRs by microbial molecules or their mimetic might become a new strategy for HIV therapy or prevention.

UR - http://www.scopus.com/inward/record.url?scp=77958464785&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77958464785&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0012831

DO - 10.1371/journal.pone.0012831

M3 - Article

C2 - 20862220

AN - SCOPUS:77958464785

VL - 5

SP - 1

EP - 12

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 9

M1 - e12831

ER -