TLR3 Modulates the Response of NK Cells against <i>Schistosoma japonicum</i>

Qu, Jiale; Li, Lü; Xie, Hongyan; Zhang, Xiaona; Yang, Quan; Qiu, Huaina; Feng, Yuanfa; Jin, Chenxi; Dong, Ning; Huang, Jun

doi:10.1155/2018/7519856

Cited by 13 publications

(11 citation statements)

References 38 publications

(44 reference statements)

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“…Signaling through MyD88 is crucial for host defense as the MyD88 pathway is vital not only for Toll-like receptors (TLRs), but is also required by the members of the interleukin-1 cytokine family, including IL-18 and IL-33 (82,83). Although, the expression of several TLRs on murine NK cells has been suggested, their roles in viral infection have not been clearly demonstrated (84). However, mice deficient in MyD88 have NK cells with defective IFN-g production and are susceptible to infections (46,85,86).…”

Section: Discussionmentioning

confidence: 99%

Expression of Nutrient Transporters on NK Cells During Murine Cytomegalovirus Infection Is MyD88-Dependent

et al. 2021

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Natural killer (NK) cells are the predominant innate lymphocytes that provide early defense against infections. In the inflammatory milieu, NK cells modify their metabolism to support high energy demands required for their proliferation, activation, and functional plasticity. This metabolic reprogramming is usually accompanied by the upregulation of nutrient transporter expression on the cell surface, leading to increased nutrient uptake required for intense proliferation. The interleukin-1 family members of inflammatory cytokines are critical in activating NK cells during infection; however, their underlying mechanism in NK cell metabolism is not fully elucidated. Previously, we have shown that IL-18 upregulates the expression of solute carrier transmembrane proteins and thereby induces a robust metabolic boost in NK cells. Unexpectedly, we found that IL-18 signaling is dispensable during viral infection in vivo, while the upregulation of nutrient transporters is primarily MyD88-dependent. NK cells from Myd88-/- mice displayed significantly reduced surface expression of nutrient receptors and mTOR activity during MCMV infection. We also identified that IL-33, another cytokine employing MyD88 signaling, induces the expression of nutrient transporters but requires a pre-exposure to IL-12. Moreover, signaling through the NK cell activating receptor, Ly49H, can also promote the expression of nutrient transporters. Collectively, our findings revealed multiple pathways that can induce the expression of nutrient transporters on NK cells while highlighting the imperative role of MyD88 in NK cell metabolism during infection.

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Section: Discussionmentioning

confidence: 99%

Expression of Nutrient Transporters on NK Cells During Murine Cytomegalovirus Infection Is MyD88-Dependent

et al. 2021

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“…Poly I:C attenuates liver fibrosis in vivo partly through enhancing TLR3-induced NK cell cytotoxicity (27,28), selectively killing activated HSCs (17). Poly I:C, as a TLR3 agonist, has been shown to have multiple biological functions in various liver diseases such as HCV infection (29), HBV infection (30), and liver cancer (31), as well as in the hepatocarcinogenesis process (32).…”

Section: Discussionmentioning

confidence: 99%

TLR3 Mediates Senescence and Immunosurveillance of Hepatic Stellate Cells

Zhou

Bei

et al. 2021

Hepat Mon

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Background: Activation of hepatic stellate cells (HSCs) is an important driver of liver fibrosis, which is a health problem of global concern, and there is no effective solution for it at the present. Senescent activated HSCs are preferentially killed by natural killer cells (NK cells) to promote the regression of hepatic fibrosis. Objectives: The purpose of this study was to investigate the effect of polyinosinic-polycytidylic acid (poly I:C) on HSCs’ senescence, a trigger for NK cell-induced cytotoxicity. Methods: The senescence of HSCs was assessed by western blot, qRT-PCR, and flow cytometry, and NK cell cytotoxicity was assessed in a co-culture of NK cells with poly I:C-treated HSCs by measuring CD107a expression. Results: The expression of p16, p21, SA-β-gal, MICA/MICB, and ULBP2 increased in poly I:C-treated HSCs, rendering them significantly susceptible to NK cell cytotoxicity. Conclusions: Poly I:C induces cellular senescence in HSCs and triggers NK cell immunosurveillance, suggesting that the role of poly I:C in HSC senescence may promote fibrosis regression.

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“…TLRs represent one of the most studied pattern recognition receptor (PRR) families (Harris et al 2006;Tartey and Takeuchi 2017). Qu demonstrated that TLR3 is the primary molecule which modulates the activation and function of NK cells during Schistosoma japonicum (S. japonicum) infection in mice (Qu et al 2018). The expression levels of TLR3 on different pulmonary lymphocytes were increased after S. japonicum infection (Chen et al 2019).…”

Section: Discussionmentioning

confidence: 99%

Effects of TLR agonists on immune responses in Trichinella spiralis infected mice

et al. 2020

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Human trichinellosis is acquired by eating raw or undercooked meats carrying muscle larvae of Trichinella spp. Toll-like receptors (TLRs) are essential components of the innate immune system. However, little is known about the potential application of TLR agonists for immunotherapy against Trichinella spiralis (T. spiralis) infection. Here, we evaluated the effects of four TLR agonists (i.e., TLR3, TLR4, TLR8, and TLR9 agonists) on T. spiralis infection in mice. The reduction rate of worm burden showed that TLR3 agonist poly(I:C) significantly reduced T. spiralis infection rather than TLR4, TLR8, and TLR9 agonists (p < 0.05). Moreover, TLR3 showed a continuous high-level of expression during 6-35 days post infection (dpi). The levels of interferon-gamma (IFN-γ), interleukin (IL)-2, and IL-6 increased significantly in mice serum compared with control group after treatment with TLR3 agonist at 0, 3, 6, 9, 12, 15, 18, 21, 28, and 35 dpi (p < 0.05). A significant decreasing trend was also detected in levels of IL-10 and IL-4 after treatment with TLR3 agonist compared with control group at 0, 3, 6, 9, 12, 15, 18, 21, 28, and 35 dpi (p < 0.05). Overall, this study suggested that TLR3-targeted therapies might be effective on worm burden reduction by regulation of the cytokine levels in the mice infected with T. spiralis.

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TLR3 Modulates the Response of NK Cells against Schistosoma japonicum

Cited by 13 publications

References 38 publications

Expression of Nutrient Transporters on NK Cells During Murine Cytomegalovirus Infection Is MyD88-Dependent

Expression of Nutrient Transporters on NK Cells During Murine Cytomegalovirus Infection Is MyD88-Dependent

TLR3 Mediates Senescence and Immunosurveillance of Hepatic Stellate Cells

Effects of TLR agonists on immune responses in Trichinella spiralis infected mice

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