Stimulation of toll-like receptor 2 in mononuclear cells from HIV-infected patients induces chemokine responses: possible pathogenic consequences.
Toll-like receptor 2 (TLR2) stimulation in monocytes may contribute to enhanced inflammation and viral replication in HIV infection. In the present study we examined if TLR2 stimulation could modulate chemokine responses in peripheral blood mononuclear cells (PBMC) from HIV-infected patients and healthy controls. Our main findings were, with similar qualitative patterns in both healthy controls and HIV-infected patients: (1) TLR2 stimulation induced up-regulation of several chemokines at the mRNA level as well as increased protein levels of macrophage inflammatory protein (MIP)-1alpha, interleukin (IL)-8 and regulated on activation, normal T cell expressed and secreted (RANTES); (2) TLR2 stimulation induced enhanced protein expression of CCR5 (a receptor for MIP-1alpha and RANTES) on monocytes; (3) In vitro stimulation with RANTES induced release of MIP-1alpha, MCP-1, IL-8 and interferon-gamma from PBMC. While increased levels of beta-chemokines possibly have antiviral effects, TLR2 stimulation may also promote a chemokine-driven inflammatory loop, potentially contributing to the immunopathogenesis of HIV infection.
Heggelund
L
L
Section of Clinical Immunology and Infectious Diseases, Medical Department, Rikshospitalet University Hospital, Univerity of Oslo, Oslo, Norway. lars.heggelund@medisin.uio.no
Damås
J K
JK
Yndestad
A
A
Holm
A M
AM
Mūller
F
F
Lien
E
E
Espevik
T
T
Aukrust
P
P
Frøland
S S
SS
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D018932:Chemokine CCL2 / Q000276:immunology; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000032:analysis; D018925:Chemokines / Q000276:immunology*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D016209:Interleukin-8 / Q000032:analysis / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D019402:Macrophage Inflammatory Proteins / Q000032:analysis / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology*; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D012367:RNA, Viral / Q000032:analysis; D019713:Receptors, CCR5 / Q000032:analysis; D011956:Receptors, Cell Surface / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D015854:Up-Regulation / Q000276:immunology
D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D018925:Chemokines; D016209:Interleukin-8; D019402:Macrophage Inflammatory Proteins; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D012367:RNA, Viral; D019713:Receptors, CCR5; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D007371:Interferon-gamma