Double‐faced implication of CD4⁺Foxp3⁺ regulatory T cells expanded by acute dengue infection via TLR2/MyD88 pathway

Abstract

Dengue infection causes dengue fever (DF) and dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). CD4 + Foxp3 + Tregs are expanded in patients during dengue infection, and appear to be associated with clinical severity. However, molecular pathways involved in Treg proliferation and the reason for their insufficient control of severe diseases are poorly understood. Here, dengue infection induced the proliferation of functional CD4 + Foxp3 + Tregs via TLR2/MyD88 pathway. Surface TLR2 on Tregs was responsible for their proliferation, and dengue-expanded Tregs subverted in vivo differentiation of effector CD8 + T cells. An additional interesting finding was that dengue-infected hosts displayed changed levels of susceptibility to other diseases in TLR2-dependent manner. This change included enhanced susceptibility to tumors and bacterial infection, but highly enhanced resistance to viral infection. Further, the transfer of dengue-proliferated Tregs protected the recipients from dengue-induced DHF/DSS and LPS-induced sepsis. In contrast, dengue-infected hosts were more susceptible to sepsis, an effect attributable to early TLR2-dependent production of proinflammatory cytokines. These facts may explain the reason why in some patients, dengue-proliferated Tregs is insufficient to control DF and DHF/DSS. Also, our observations lead to new insights into Treg responses activated by dengue infection in a TLR2-dependent manner, which could differentially act on subsequent exposure to other disease-producing situations.

Aspergillus fumigatus change Gasdermin-D-dependent pyrolysis of the lung through regulating TRL2-dependent Regulatory T cells differentiation

“…As shown in Fig. 4A, Treg cells ratio in the spleen of TLR2 −/− mice were signi cantly lower than those in the WT mice, this is consistent with previous research(P < 0.0001) (George et al 2020). We also tested the expression of Foxp3 in the lungs of mice after infection with A.…”

“…Study showing that C. albicans results in immunosuppression via TLR2-derived signals that mediate increased IL-10 production and survival of Treg cells[ (Netea et al 2004)]. And current evidence showed that Dengue infection in uenced the proliferation of Treg cells through TLR2/MyD88 pathway [(George et al 2020)]. In our study, we found that TLR2 de cient mice have a signi cant decrease in Tregs of spleen ( Fig.…”

“…On the other hand, regulatory T cells (Tregs) role in promoting immune tolerance and immune escape by restraining the body's immune response is concerned. It could increase the sensitivity of bacterial infections[ (George et al 2020)]. In a mouse model used to understand infection caused by A. fumigatus it was revealed that Tregs increase is evident [(Wang et al 2017)].…”

“…The function of T cells is regulated by how they provoke the expression of TLRs [(George et al 2017)]. The TLR2 on the cell membrane of Tregs is responsible for its proliferation, the proliferation of CD4 + Foxp3 + Treg cells can be induced by TLR2/MyD88 pathway in Dengue infection [(George et al 2020)]. In a mouse test to analyze infection caused by Candida albicans, reducing the expression of TLR2 lowers the quantity of CD4 + CD25 + Treg cells and decrease the fungal burden [(Netea et al 2004)].…”

The Protective Effects of <b><i>Helicobacter pylori</i></b> Infection on Allergic Asthma

“…Different TLRs have different functions [82][83][84]. TLR2 is an important pattern recognition receptor in Tregs [85,86] and TLR9 mainly plays a negative role in the regulation of allergic inflammation [87][88][89]. TLR4 not only relies on conserved sequences encoded by embryological genes to identify pathogenic microorganisms and activate innate immunity but also regulates adaptive immunity [90,91].…”