Activation of the formyl peptide receptor by the HIV-derived peptide T-20 suppresses interleukin-12 p70 production by human monocytes.
It has been proposed that in the early stages of human immunodeficiency (HIV) infection, before the loss of CD4(+) T cells, inhibition of IL-12 production from host antigen-presenting cells plays a critical role in the suppression of T-helper cell type 1 responses. Activation of the G(i)-protein-coupled high-affinity N-formyl peptide receptor by f-met-leu-phe and HIV-derived peptide T-20-suppressed IL-12 p70 production from human monocytes in response to both T-cell-dependent and T-cell-independent stimulation are reported. Activation of the low-affinity N-formyl peptide receptor by the HIV-derived F-peptide suppressed IL-12 production more modestly. This suppression was pertussis toxin sensitive and was selective for IL-12; the production of IL-10, transforming growth factor-beta, and tumor necrosis factor-alpha was unaltered. The production of IL-12 p70 by dendritic cells was unaffected by these peptides despite functional expression of the high-affinity fMLP receptor. These findings provide a potential direct mechanism for HIV-mediated suppression of IL-12 production and suggest a broader role for G-protein-coupled receptors in the regulation of innate immune responses. (Blood. 2001;97:3531-3536)
Braun
M C
MC
Immune Cell Interaction Unit, Mucosal Immunity Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Wang
J M
JM
Lahey
E
E
Rabin
R L
RL
Kelsall
B L
BL
D000595:Amino Acid Sequence; D023201:CD40 Ligand / Q000494:pharmacology; D003713:Dendritic Cells / Q000378:metabolism; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000502:physiology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D015700:HIV Envelope Protein gp41 / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000235:genetics; D015847:Interleukin-4 / Q000494:pharmacology; D008969:Molecular Sequence Data; D009000:Monocytes / Q000378:metabolism*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D037342:Pertussis Toxin; D012333:RNA, Messenger / Q000032:analysis; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000032:analysis / Q000187:drug effects* / Q000502:physiology*; D018000:Receptors, Peptide / Q000032:analysis / Q000187:drug effects* / Q000502:physiology*; D015398:Signal Transduction; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D015700:HIV Envelope Protein gp41; D009842:Oligopeptides; D010446:Peptide Fragments; D012333:RNA, Messenger; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D018000:Receptors, Peptide; D010566:Virulence Factors, Bordetella; D023201:CD40 Ligand; D018664:Interleukin-12; D015847:Interleukin-4; D009240:N-Formylmethionine Leucyl-Phenylalanine; C021642:F-chemotactic peptide; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D037342:Pertussis Toxin; D019206:GTP-Binding Protein alpha Subunits, Gi-Go