Mumps virus induces innate immune responses in mouse ovarian granulosa cells through the activation of Toll-like receptor 2 and retinoic acid-inducible gene I

2016 ◽  
Vol 436 ◽  
pp. 183-194 ◽  
Author(s):  
Qing Wang ◽  
Han Wu ◽  
Lijing Cheng ◽  
Keqin Yan ◽  
Lili Shi ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Immune Responses ◽  
Granulosa Cells ◽  
Mumps Virus ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Toll Like Receptor ◽  
Ovarian Granulosa Cells ◽  
Toll Like Receptor 2 ◽  
Inducible Gene

scholarly journals Cytosolic DNA sensor-initiated innate immune responses in mouse ovarian granulosa cells

Reproduction ◽  
2017 ◽  
Vol 153 (6) ◽  
pp. 821-834 ◽  
Author(s):  
Keqin Yan ◽  
Dingqing Feng ◽  
Jing Liang ◽  
Qing Wang ◽  
Lin Deng ◽  
...  
Keyword(s):  
Immune Responses ◽  
Granulosa Cells ◽  
Innate Immune ◽  
Type I Interferons ◽  
Endocrine Function ◽  
Type I ◽  
Dna Sensor ◽  
Innate Immune Responses ◽  
Oligoadenylate Synthetase ◽  
Ovarian Granulosa Cells

Viral infections of the ovary may perturb ovarian functions. However, the mechanisms underlying innate immune responses in the ovary are poorly understood. The present study demonstrates that cytosolic viral DNA sensor signaling initiates the innate immune response in mouse ovarian granulosa cells and affects endocrine function. The cytosolic DNA sensors p204 and cGAS and their common signaling adaptor stimulator of interferon (IFN) genes (STING) were constitutively expressed in granulosa cells. Transfection with VACV70, a synthetic vaccinia virus (VACV) DNA analog, induced the expression of type I interferons (IFNA/B) and major inflammatory cytokines (TNFA and IL6) through IRF3 and NF-κB activation respectively. Moreover, several IFN-inducible antiviral proteins, including 2′,5′-oligoadenylate synthetase, IFN-stimulating gene 15 and Mx GTPase 1, were also induced by VACV70 transfection. The innate immune responses in granulosa cells were significantly reduced by the transfection of specific small-interfering RNAs targeting p204, cGas or Sting. Notably, the VACV70-triggered innate immune responses affected steroidogenesis in vivo and in vitro. The data presented in this study describe the mechanism underlying ovarian immune responses to viral infection.

Innate immune responses to toll-like receptor stimulation are altered during the course of pregnancy

2018 ◽  
Vol 128 ◽  
pp. 30-37 ◽  
Author(s):  
Susanne Maria Ziegler ◽  
Cai Niklaas Feldmann ◽  
Sven Hendrik Hagen ◽  
Laura Richert ◽  
Tanja Barkhausen ◽  
...  
Keyword(s):  
Immune Responses ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Toll Like Receptor ◽  
Receptor Stimulation

scholarly journals Toll-Like Receptor-Triggered Calcium Mobilization Protects Mice against Bacterial Infection through Extracellular ATP Release

2014 ◽  
Vol 82 (12) ◽  
pp. 5076-5085 ◽  
Author(s):  
Hua Ren ◽  
Yunfei Teng ◽  
Binghe Tan ◽  
Xiaoyu Zhang ◽  
Wei Jiang ◽  
...  
Keyword(s):  
Immune Responses ◽  
Pyridoxal Phosphate ◽  
Atp Release ◽  
Extracellular Atp ◽  
Calcium Mobilization ◽  
Innate Immune ◽  
Disulfonic Acid ◽  
Dependent Manner ◽  
Innate Immune Responses ◽  
Toll Like Receptor

ABSTRACTExtracellular ATP (eATP), released as a “danger signal” by injured or stressed cells, plays an important role in the regulation of immune responses, but the relationship between ATP release and innate immune responses is still uncertain. In this study, we demonstrated that ATP was released through Toll-like receptor (TLR)-associated signaling in bothEscherichia coli-infected mice and lipopolysaccharide (LPS)- or Pam3CSK4-treated macrophages. This ATP release could be blocked completely only byN-ethylmaleimide (NEM), not by carbenoxolone (CBX), flufenamic acid (FFA), or probenecid, suggesting the key role of exocytosis in this process. Furthermore, LPS-induced ATP release could also be reduced dramatically through suppressing calcium mobilization by use of U73122, caffeine, and thapsigargin (TG). In addition, the secretion of interleukin-1β (IL-1β) and CCL-2 was enhanced significantly by ATP, in a time- and dose-dependent manner. Meanwhile, macrophage-mediated phagocytosis of bacteria was also promoted significantly by ATP stimulation. Furthermore, extracellular ATP reduced the number of invading bacteria and protected mice from peritonitis by activating purinergic receptors. Mechanistically, phosphorylation of AKT and ERK was overtly increased by ATP in antibacterial immune responses. Accordingly, if we blocked the P2X- and P2Y-associated signaling pathway by using suramin and pyridoxal phosphate-6-azo(benzene-2,4-disulfonic acid), tetrasodium salt (PPADS), the ATP-enhanced immune response was restrained significantly. Taken together, our findings reveal an internal relationship between danger signals and TLR signaling in innate immune responses, which suggests a potential therapeutic significance of calcium mobilization-mediated ATP release in infectious diseases.

scholarly journals Toll-like Receptor 7 Contributes to Inflammation, Organ Injury, and Mortality in Murine Sepsis

2019 ◽  
Vol 131 (1) ◽  
pp. 105-118 ◽  
Author(s):  
Wenling Jian ◽  
Lili Gu ◽  
Brittney Williams ◽  
Yan Feng ◽  
Wei Chao ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Immune Responses ◽  
Knockout Mice ◽  
Cecal Ligation ◽  
Kidney Injury ◽  
Innate Immune ◽  
Organ Injury ◽  
Innate Immune Responses ◽  
Toll Like Receptor ◽  
Wild Type

Abstract Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Sepsis remains a critical illness with high mortality. The authors have recently reported that mouse plasma RNA concentrations are markedly increased during sepsis and closely associated with its severity. Toll-like receptor 7, originally identified as the sensor for single-stranded RNA virus, also mediates host extracellular RNA-induced innate immune responses in vitro and in vivo. Here, the authors hypothesize that innate immune signaling via Toll-like receptor 7 contributes to inflammatory response, organ injury, and mortality during polymicrobial sepsis. Methods Sepsis was created by (1) cecal ligation and puncture or (2) stool slurry peritoneal injection. Wild-type and Toll-like receptor 7 knockout mice, both in C57BL/6J background, were used. The following endpoints were measured: mortality, acute kidney injury biomarkers, plasma and peritoneal cytokines, blood bacterial loading, peritoneal leukocyte counts, and neutrophil phagocytic function. Results The 11-day overall mortality was 81% in wild-type mice and 48% in Toll-like receptor 7 knockout mice after cecal ligation and puncture (N = 27 per group, P = 0.0031). Compared with wild-type septic mice, Toll-like receptor 7 knockout septic mice also had lower sepsis severity, attenuated plasma cytokine storm (wild-type vs. Toll-like receptor 7 knockout, interleukin-6: 43.2 [24.5, 162.7] vs. 4.4 [3.1, 12.0] ng/ml, P = 0.003) and peritoneal inflammation, alleviated acute kidney injury (wild-type vs. Toll-like receptor 7 knockout, neutrophil gelatinase-associated lipocalin: 307 ± 184 vs.139 ± 41-fold, P = 0.0364; kidney injury molecule-1: 40 [16, 49] vs.13 [4, 223]-fold, P = 0.0704), lower bacterial loading, and enhanced leukocyte peritoneal recruitment and phagocytic activities at 24 h. Moreover, stool slurry from wild-type and Toll-like receptor 7 knockout mice resulted in similar level of sepsis severity, peritoneal cytokines, and leukocyte recruitment in wild-type animals after peritoneal injection. Conclusions Toll-like receptor 7 plays an important role in the pathogenesis of polymicrobial sepsis by mediating host innate immune responses and contributes to acute kidney injury and mortality.

scholarly journals Toll-Like Receptor 4 Mediates Innate Immune Responses to Haemophilus influenzae Infection in Mouse Lung

2002 ◽  
Vol 168 (2) ◽  
pp. 810-815 ◽  
Author(s):  
Xiaorong Wang ◽  
Christian Moser ◽  
Jean-Pierre Louboutin ◽  
Elena S. Lysenko ◽  
Daniel J. Weiner ◽  
...  
Keyword(s):  
Immune Responses ◽  
Haemophilus Influenzae ◽  
Innate Immune ◽  
Mouse Lung ◽  
Innate Immune Responses ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4
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