TLR2 Signaling Renders Quiescent Naive and Memory CD4+ T Cells More Susceptible to Productive Infection with X4 and R5 HIV-Type 1

Abstract

It has been recently demonstrated that circulating microbial products are responsible for a systemic immune activation in individuals infected with HIV-type 1. Bacterial products carry structural conserved motifs recognized by TLRs. Some TLR members are expressed in primary human CD4+ T cells but the precise functional role played by these pattern recognition receptors is still imprecise. In this study, we report that engagement of TLR2 in quiescent naive and memory CD4+ T cells leads to the acquisition of an effector-like phenotype. Interestingly, engagement of TLR2 renders both cell subsets more susceptible to productive infection with X4 virions and a higher virus production was seen with R5 viruses. It can be proposed that exposure of resting CD4+ T cells to pathogen-derived products that can engage TLR2 induces the acquisition of an effector-like phenotype in naive and memory CD4+ T lymphocytes, a phenomenon that might result in an acceleration of virus replication, immune dysregulation, and HIV-type 1-mediated disease progression.

Activated Human Neonatal CD8+ T Cells Are Subject to Immunomodulation by Direct TLR2 or TLR5 Stimulation

“…ϩ T cells independently of TCR sensitization has been observed (45). A similar effect on neonatal naive CD8 ϩ T cells was observed during the course of our study (data not shown).…”

“…The direct action of TLR9-triggered murine CD4 ϩ T cells in enhancing humoral immunity by causing increased Ig titers has also been described (42). An indirect association with human disease has also been posited through the demonstration of alterations in the expression of various TLRs on T cell subsets between healthy and ill humans during filarial (43), hepatitis C (44), and HIV (45) infections.…”

TNF-α and TLR agonists increase susceptibility to HIV-1 transmission by human Langerhans cells ex vivo

“…Although HIV-1 was observed in intracellular vesicles, cell-bound HIV-1 was primarily transmitted after Pam3CSK4 stimulation. Pam3CSK4 might upregulate the expression of receptors that increase HIV-1 capture, such as heparan sulfate proteoglycans (46) (47). However, we observed increased trans-infection, which is independent of fusion of HIV-1 with LCs, strongly suggesting that increased HIV-1 capture but not infection is responsible for transmission after Pam3CSK4 stimulation.…”

Nuclear Receptor Signaling Inhibits HIV-1 Replication in Macrophages through Multipletrans-Repression Mechanisms

“…Second, STIs cause inflammation that leads to the recruitment of immune cells to the site of inflammation, thereby increasing the size of the HIV-1 target cell population (88,128,136). Third, STIs promote a favorable local environment for HIV-1 replication both by directly activating HIV-1 target cells and by inducing the release of cytokines that favor virus replication through the engagement of Toll-like receptors (TLRs) and other innate immune sensors in cells present in the mucosa (9,10,37,57,75,122,134,145,146,161).…”