Estrogen Suppresses Cytokines Release in cc4821 Neisseria meningitidis Infection via TLR4 and ERβ-p38-MAPK Pathway

Guo, Pengbo; Xu, Juan; Liang, Hao; Xu, Li; Gao, Wanying; Chen, Ziman; Gao, Yuan; Zhang, Maojun; Guo, Yu; Shao, Zhujun

doi:10.3389/fmicb.2022.834091

Cited by 3 publications

(2 citation statements)

References 30 publications

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“…Protein homoeostasis is critically important for basic cellular signalling and different pathogens target these molecules to highjack host cellular machinery (Guo et al., 2022 ; Horianopoulos et al., 2021 ). AKT degradation can induce p85‐PI3 kinase (PI3K) and inhibit PI3K signalling pathway (Xu et al., 2021 ).…”

Section: Resultsmentioning

confidence: 99%

Taenia solium cysticerci's extracellular vesicles Attenuate the AKT/mTORC1 pathway for Alleviating DSS‐induced colitis in a murine model

Rawat,

Keshri,

Arora

et al. 2024

J of Extracellular Vesicle

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The excretory–secretory proteome plays a pivotal role in both intercellular communication during disease progression and immune escape mechanisms of various pathogens including cestode parasites like Taenia solium. The cysticerci of T. solium causes infection in the central nervous system known as neurocysticercosis (NCC), which affects a significant population in developing countries. Extracellular vesicles (EVs) are 30–150‐nm‐sized particles and constitute a significant part of the secretome. However, the role of EV in NCC pathogenesis remains undetermined. Here, for the first time, we report that EV from T. solium larvae is abundant in metabolites that can negatively regulate PI3K/AKT pathway, efficiently internalized by macrophages to induce AKT and mTOR degradation through auto‐lysosomal route with a prominent increase in the ubiquitination of both proteins. This results in less ROS production and diminished bacterial killing capability among EV‐treated macrophages. Due to this, both macro‐autophagy and caspase‐linked apoptosis are upregulated, with a reduction of the autophagy substrate sequestome 1. In summary, we report that T. solium EV from viable cysts attenuates the AKT–mTOR pathway thereby promoting apoptosis in macrophages, and this may exert immunosuppression during an early viable stage of the parasite in NCC, which is primarily asymptomatic. Further investigation on EV‐mediated immune suppression revealed that the EV can protect the mice from DSS‐induced colitis and improve colon architecture. These findings shed light on the previously unknown role of T. solium EV and the therapeutic role of their immune suppression potential.

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Section: Resultsmentioning

confidence: 99%

Taenia solium cysticerci's extracellular vesicles Attenuate the AKT/mTORC1 pathway for Alleviating DSS‐induced colitis in a murine model

Rawat,

Keshri,

Arora

et al. 2024

J of Extracellular Vesicle

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“…Consistently, Guo et al. showed that 17 β-estradiol (E2) suppressed the release of inflammatory factors via inhibiting TLR4 ( 70 ). Therefore, there is a negative relationship between estrogen and TLR4 expression.…”

Section: Clinical Significances Of Tlr4 In Osteoporosismentioning

confidence: 87%

The critical role of toll-like receptor 4 in bone remodeling of osteoporosis: from inflammation recognition to immunity

Zhu,

Du,

Zhang

et al. 2024

Front. Immunol.

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Osteoporosis is a common chronic metabolic bone disorder. Recently, increasing numbers of studies have demonstrated that Toll-like receptor 4 (TLR4, a receptor located on the surface of osteoclasts and osteoblasts) plays a pivotal role in the development of osteoporosis. Herein, we performed a comprehensive review to summarize the findings from the relevant studies within this topic. Clinical data showed that TLR4 polymorphisms and aberrant TLR4 expression have been associated with the clinical significance of osteoporosis. Mechanistically, dysregulation of osteoblasts and osteoclasts induced by abnormal expression of TLR4 is the main molecular mechanism underlying the pathological processes of osteoporosis, which may be associated with the interactions between TLR4 and NF-κB pathway, proinflammatory effects, ncRNAs, and RUNX2. In vivo and in vitro studies demonstrate that many promising substances or agents (i.e., methionine, dioscin, miR-1906 mimic, artesunate, AEG-1 deletion, patchouli alcohol, and Bacteroides vulgatus) have been able to improve bone metabolism (i.e., inhibits bone resorption and promotes bone formation), which may partially attribute to the inhibition of TLR4 expression. The present review highlights the important role of TLR4 in the clinical significance and the pathogenesis of osteoporosis from the aspects of inflammation and immunity. Future therapeutic strategies targeting TLR4 may provide a new insight for osteoporosis treatment.

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Exosomes from Taenia solium cysticerci impairs PI3K-AKT-mTOR pathway and induces apoptosis in macrophages

rawat,

Keshri,

Arora

et al. 2024

Preprint

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Exosomes are extracellular vesicles of 30-100nm which constitutes significant part of secretome. Excretory secretory proteome plays significant role in pathogenesis and immune escapes mechanisms of complex parasites like Taenia solium. The cyst of T. solium causes infection to CNS i.e., neurocysticercosis (NCC) a neglected tropical disease. However, the role of exosomes in NCC pathogenesis is not understood till now. Here for the first time, we report exosomes- induce AKT degradation in macrophages via the autophagosomal-lysosomal pathway but not via the proteasomal pathway. The phenotype is supported by the low ROS production with impaired bacterial killing. Along with this PI3K pathway was also seen to be impaired after exosome stimulation in macrophages. We also found mTOR degradation was via the lysosomal pathway with a notable increase in the ubiquitination. Following this autophagy and apoptosis both increased with significant degradation of autophagy substrate SQSTM1. In summary, here we report that the T. solium exosomes modulate PI3K-AKT-mTOR pathway to induce autophagy and apoptosis in macrophages and this may exert immunosuppression via the exosomes during NCC disease. These finding helps us to understand the immune suppression induced by cyst for its survival in host.

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Estrogen Suppresses Cytokines Release in cc4821 Neisseria meningitidis Infection via TLR4 and ERβ-p38-MAPK Pathway

Cited by 3 publications

References 30 publications

Taenia solium cysticerci's extracellular vesicles Attenuate the AKT/mTORC1 pathway for Alleviating DSS‐induced colitis in a murine model

Taenia solium cysticerci's extracellular vesicles Attenuate the AKT/mTORC1 pathway for Alleviating DSS‐induced colitis in a murine model

The critical role of toll-like receptor 4 in bone remodeling of osteoporosis: from inflammation recognition to immunity

Exosomes from Taenia solium cysticerci impairs PI3K-AKT-mTOR pathway and induces apoptosis in macrophages

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