TLRs trigger innate immunity that recognizes conserved motifs of invading pathogens, resulting in cellular activation and release of inflammatory factors. The influence of TLR activation on resistance to HIV-1 infection has not been investigated in HIV-1 exposed seronegative (ESN) individuals. PBMCs isolated from heterosexually ESN individuals were stimulated with agonists specific for TLR3 (poly I:C), TLR4 (LPS), TLR7 (imiquimod), and TLR7/8 (ssRNA40). We evaluated expression of factors involved in TLR signaling cascades, production of downstream effector immune mediators, and TLR-expression in CD4+ and CD14+ cells. Results were compared with those obtained in healthy controls (HCs). ESN individuals showed: 1) comparable percentages of CD14+/TLR4+ and CD4+/TLR8+ CD14+/TLR8+ cells; 2) higher responsiveness to poly I:C, LPS, imiquimod, and ssRNA40 stimulation, associated with significantly increased production of IL-1beta, IL-6, TNF-alpha, and CCL3; 3) augmented expression of mRNA specific for other targets (CCL2, CSF3, CSF2, IL-1alpha, IL-8, IL-10, IL-12, cyclooxygenase 2) demonstrated by broader TLRs pathway expression analyses; and 4) increased MyD88/MyD88s(short) ratio, mainly following TLR7/8 stimulation. We also compared TLR-agonist-stimulated cytokine/chemokine production in CD14+ PBMCs and observed decreased IFN-beta production in ESN individuals compared with HCs upon TLR7/8-agonist stimulation. These data suggest that TLR stimulation in ESN individuals results in a more robust release of immunologic factors that can influence the induction of stronger adaptive antiviral immune responses and might represent a virus-exposure-induced innate immune protective phenotype against HIV-1.
TLR activation pathways in HIV-1-exposed seronegative individuals / M. Biasin, L. Piacentini, S. Lo Caputo, V. Naddeo, P. Pierotti, M. Borelli, D. Trabattoni, F. Mazzotta, G.M. Shearer, M. Clerici. - In: JOURNAL OF IMMUNOLOGY. - ISSN 0022-1767. - 184:5(2010 Mar 01), pp. 2710-2717.
|Titolo:||TLR activation pathways in HIV-1-exposed seronegative individuals|
BIASIN, MARA (Primo)
PIACENTINI, LUCA (Secondo)
CLERICI, MARIO SALVATORE (Ultimo)
|Settore Scientifico Disciplinare:||Settore MED/04 - Patologia Generale|
|Data di pubblicazione:||1-mar-2010|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.4049/jimmunol.0902463|
|Appare nelle tipologie:||01 - Articolo su periodico|