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TLR activation pathways in HIV-1-exposed seronegative individuals.
J Immunol 2010; 184(5):2710-7JI

Abstract

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.

Authors+Show Affiliations

Cattedra di Immunologia, Università degli Studi di Milano, Milan, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20124101

Citation

Biasin, Mara, et al. "TLR Activation Pathways in HIV-1-exposed Seronegative Individuals." Journal of Immunology (Baltimore, Md. : 1950), vol. 184, no. 5, 2010, pp. 2710-7.
Biasin M, Piacentini L, Lo Caputo S, et al. TLR activation pathways in HIV-1-exposed seronegative individuals. J Immunol. 2010;184(5):2710-7.
Biasin, M., Piacentini, L., Lo Caputo, S., Naddeo, V., Pierotti, P., Borelli, M., ... Clerici, M. (2010). TLR activation pathways in HIV-1-exposed seronegative individuals. Journal of Immunology (Baltimore, Md. : 1950), 184(5), pp. 2710-7. doi:10.4049/jimmunol.0902463.
Biasin M, et al. TLR Activation Pathways in HIV-1-exposed Seronegative Individuals. J Immunol. 2010 Mar 1;184(5):2710-7. PubMed PMID: 20124101.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - TLR activation pathways in HIV-1-exposed seronegative individuals. AU - Biasin,Mara, AU - Piacentini,Luca, AU - Lo Caputo,Sergio, AU - Naddeo,Valentina, AU - Pierotti,Piera, AU - Borelli,Manuela, AU - Trabattoni,Daria, AU - Mazzotta,Francesco, AU - Shearer,Gene M, AU - Clerici,Mario, Y1 - 2010/02/01/ PY - 2010/2/4/entrez PY - 2010/2/4/pubmed PY - 2010/5/5/medline SP - 2710 EP - 7 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J. Immunol. VL - 184 IS - 5 N2 - 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. SN - 1550-6606 UR - https://www.unboundmedicine.com/medline/citation/20124101/TLR_activation_pathways_in_HIV_1_exposed_seronegative_individuals_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=20124101 DB - PRIME DP - Unbound Medicine ER -