Skip to main content

HIV-1 activates macrophages independent of Toll-like receptors.

Publication ,  Journal Article
Brown, JN; Kohler, JJ; Coberley, CR; Sleasman, JW; Goodenow, MM
Published in: PLoS One
2008

BACKGROUND: Macrophages provide an interface between innate and adaptive immunity and are important long-lived reservoirs for Human Immunodeficiency Virus Type-1 (HIV-1). Multiple genetic networks involved in regulating signal transduction cascades and immune responses in macrophages are coordinately modulated by HIV-1 infection. METHODOLOGY/PRINCIPAL FINDINGS: To evaluate complex interrelated processes and to assemble an integrated view of activated signaling networks, a systems biology strategy was applied to genomic and proteomic responses by primary human macrophages over the course of HIV-1 infection. Macrophage responses, including cell cycle, calcium, apoptosis, mitogen-activated protein kinases (MAPK), and cytokines/chemokines, to HIV-1 were temporally regulated, in the absence of cell proliferation. In contrast, Toll-like receptor (TLR) pathways remained unaltered by HIV-1, although TLRs 3, 4, 7, and 8 were expressed and responded to ligand stimulation in macrophages. HIV-1 failed to activate phosphorylation of IRAK-1 or IRF-3, modulate intracellular protein levels of Mx1, an interferon-stimulated gene, or stimulate secretion of TNF, IL-1beta, or IL-6. Activation of pathways other than TLR was inadequate to stimulate, via cross-talk mechanisms through molecular hubs, the production of proinflammatory cytokines typical of a TLR response. HIV-1 sensitized macrophage responses to TLR ligands, and the magnitude of viral priming was related to virus replication. CONCLUSIONS/SIGNIFICANCE: HIV-1 induced a primed, proinflammatory state, M1(HIV), which increased the responsiveness of macrophages to TLR ligands. HIV-1 might passively evade pattern recognition, actively inhibit or suppress recognition and signaling, or require dynamic interactions between macrophages and other cells, such as lymphocytes or endothelial cells. HIV-1 evasion of TLR recognition and simultaneous priming of macrophages may represent a strategy for viral survival, contribute to immune pathogenesis, and provide important targets for therapeutic approaches.

Duke Scholars

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2008

Volume

3

Issue

12

Start / End Page

e3664

Location

United States

Related Subject Headings

  • Toll-Like Receptors
  • Macrophages
  • MAP Kinase Signaling System
  • Immunity, Innate
  • Humans
  • HIV-1
  • General Science & Technology
  • Gene Expression Profiling
  • Cell Proliferation
  • Calcium Signaling
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Brown, J. N., Kohler, J. J., Coberley, C. R., Sleasman, J. W., & Goodenow, M. M. (2008). HIV-1 activates macrophages independent of Toll-like receptors. PLoS One, 3(12), e3664. https://doi.org/10.1371/journal.pone.0003664
Brown, Joseph N., James J. Kohler, Carter R. Coberley, John W. Sleasman, and Maureen M. Goodenow. “HIV-1 activates macrophages independent of Toll-like receptors.PLoS One 3, no. 12 (2008): e3664. https://doi.org/10.1371/journal.pone.0003664.
Brown JN, Kohler JJ, Coberley CR, Sleasman JW, Goodenow MM. HIV-1 activates macrophages independent of Toll-like receptors. PLoS One. 2008;3(12):e3664.
Brown, Joseph N., et al. “HIV-1 activates macrophages independent of Toll-like receptors.PLoS One, vol. 3, no. 12, 2008, p. e3664. Pubmed, doi:10.1371/journal.pone.0003664.
Brown JN, Kohler JJ, Coberley CR, Sleasman JW, Goodenow MM. HIV-1 activates macrophages independent of Toll-like receptors. PLoS One. 2008;3(12):e3664.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2008

Volume

3

Issue

12

Start / End Page

e3664

Location

United States

Related Subject Headings

  • Toll-Like Receptors
  • Macrophages
  • MAP Kinase Signaling System
  • Immunity, Innate
  • Humans
  • HIV-1
  • General Science & Technology
  • Gene Expression Profiling
  • Cell Proliferation
  • Calcium Signaling