TLR Activation Pathways in HIV-1–Exposed Seronegative Individuals

Abstract

Material Supplementary 3.DC1http://www.jimmunol.org/content/suppl/2010/01/29/jimmunol.090246

A Common Polymorphism in TLR3 Confers Natural Resistance to HIV-1 Infection

“…This effect may at least partially be mediated by the increased production of proinflammatory cytokines by innate and activated CD69 + lymphocytes that we observed in PBMCs derived from individuals carrying the 412Phe allele after HIV-infection assay. Recently it has been reported that after HIV exposure in HESN individuals, TLR engagement results in the induction of enhanced innate and adaptive immune responses, which in turn interfere with HIV replication and productive infection (7). In line with these observations, the cytokine milieu derived from TLR3-specific stimulation in PBMCs carrying the 412Phe allele resembles the one detected after HIV infection assay.…”

“…These subjects are part of a wellcharacterized cohort of serodiscordant heterosexual couples that has been followed since 1997 (7). HESN and healthy controls were recruited at the S. Maria Annunziata Hospital (Florence, Italy); all of them were Italian of Caucasian origin.…”

“…Recently, stimulation of distinct TLRs, including TLR3, with specific agonists was shown to elicit more vigorous immune activation in HIV-1-exposed seronegative (HESN) individuals compared with that in healthy controls (7). The notion that a subset of human subjects remains uninfected despite multiple exposures to HIV-1 has been known for years (8,9).…”

Suppression of human immunodeficiency virus type 1 replication in macrophages by commensal bacteria preferentially stimulating Toll-like receptor 4

“…For example, TLR2 recognizes lipoteichoic acid (LTA), TLR3 recognizes dsRNA, TLR4 recognizes lipopolysaccharide (LPS), TLR5 recognizes flagellin, TLR7/8 recognizes ssRNA and TLR9 recognizes CpG DNA. A recent report indicated that the patterns of cytokine responses against various TLR ligands in the HIV-1-exposed seronegative individuals partly differed from those of controls (Biasin et al, 2010). Some TLR ligands have been shown to suppress HIV-1 replication.…”

Células dendríticas plasmocitóides, expressão de receptores "Toll-like" 9 e 3 e de podoplanina nas lesões cutâneas do Sarcoma de Kaposi associado à síndrome de imunodeficiência adquirida e esporádico

“…Polimorfismos da porção extracelular (ectodomínio) do TLR 3 determinam maior resistência à infecção pelo HIV (Sironi et al, 2012). Em indivíduos cronicamente expostos à infecção pelo HIV e que não apresentam soroconversão, o estímulo do TLR 3 pelo seu agonista sintético, poli(I:C) -ácido poliriboinosinicopoliribocitidílico -desencadeia maior produção de citocinas inflamatórias (Biasin et al, 2010). Além disso, a ativação do TLR 3 em macrófagos suprime a infecção e a replicação do HIV através de mecanismos dependentes de IFN tipo 1 (Zhou et al, 2010).…”