Expression of TLR4 gene is downregulated in acquired immune deficiency syndrome‑associated Kaposi's sarcoma

Lu, Xiaobo; Wan, Xuefeng; Li, Xiaoran; Pan, Kejun; Maimaitiaili, Wubuli; Zhang, Yuexin

doi:10.3892/etm.2018.6941

Cited by 1 publication

(1 citation statement)

References 31 publications

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“…The continual engagement of TLRs could lead to secondary immunosuppression to neutralize chronic proinflammatory responses and eventually favor HIV immunopathogenesis. The differential expression of TLRs in different pathological conditions of HIV/simian immunodeficiency virus (SIV) infection has been reported [ 24 , 25 ]. The trans-membrane domain of the HIV envelope directly interacts with TLR2 and attenuates TNF-α, IL-6, and MCP-1 secretions of macrophages in in vivo and in vitro models [ 26 ].…”

Section: Introductionmentioning

confidence: 99%

Toll-like Receptor 2 Mediated Immune Regulation in Simian Immunodeficiency Virus-Infected Rhesus Macaques

Boby,

Williams,

Das

et al. 2023

Vaccines

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Toll-like receptors (TLRs) are crucial to the innate immune response. They regulate inflammatory reactions by initiating the production of pro-inflammatory cytokines and chemokines. TLRs also play a role in shaping the adaptive immune responses. While this protective response is important for eliminating infectious pathogens, persistent activation of TLRs may result in chronic immune activation, leading to detrimental effects. The role of TLR2 in regulating HIV-1 infection in vivo has yet to be well described. In this study, we used an SIV-infected rhesus macaque model to simulate HIV infection in humans. We evaluated the plasma of the macaques longitudinally and found a significant increase in the soluble TLR2 (sTLR2) level after SIV infection. We also observed an increase in membrane-bound TLR2 (mb-TLR2) in cytotoxic T cells, B cells, and NK cells in PBMC and NK cells in the gut after infection. Our results suggest that sTLR2 regulates the production of various cytokines and chemokines, including IL-18, IL-1RA, IL-15, IL-13, IL-9, TPO, FLT3L, and IL-17F, as well as chemokines, including IP-10, MCP-1, MCP-2, ENA-78, GRO-α, I-TAC, Fractalkine, SDF-1α, and MIP-3α. Interestingly, these cytokines and chemokines were also upregulated after the infection. The positive correlation between SIV copy number and sTLR2 in the plasma indicated the involvement of TLR2 in the regulation of viral replication. These cytokines and chemokines could directly or indirectly regulate viral replication through the TLR2 signaling pathways. When we stimulated PBMC with the TLR2 agonist in vitro, we observed a direct induction of various cytokines and chemokines. Some of these cytokines and chemokines, such as IL-1RA, IL-9, IL-15, GRO-α, and ENA-78, were positively correlated with sTLR2 in vivo, highlighting the direct involvement of TLR2 in the regulation of the production of these factors. Our findings suggest that TLR2 expression may be a target for developing new therapeutic strategies to combat HIV infection.

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Section: Introductionmentioning

confidence: 99%