bims-inflin Biomed News
on Inflammasome and infection
Issue of 2025–01–26
two papers selected by
Juliane Cristina Ribeiro Fernandes, Faculdade de Medicina de Ribeirão Preto
  1. Activation and evasion of inflammasomes during viral and microbial infection.
  2. Activation of the COX-2/mPGES-1/PGE-2 cascade through the NLRP3 inflammasome contributes to Angiostrongylus cantonensis-induced eosinophilic meningoencephalitis.
  1. Cell Mol Life Sci. 2025 Jan 21. 82(1): 56
    Activation and evasion of inflammasomes during viral and microbial infection.
    Dan Ren, Xiaoou Ye, Ruiming Chen, Xiuzhi Jia, Xianhong He, Jinhui Tao, Tengchuan Jin, Songquan Wu, Hongliang Zhang.
      The inflammasome is a cytoplasmic multiprotein complex that induces the maturation of the proinflammatory cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18) or pyroptosis by activating caspases, which play critical roles in regulating inflammation, cell death, and various cellular processes. Multiple studies have shown that the inflammasome is a key regulator of the host defence response against pathogen infections. During the process of pathogenic microbe invasion into host cells, the host's innate immune system recognizes these microbes by activating inflammasomes, triggering inflammatory responses to clear the microbes and initiate immune responses. Moreover, microbial pathogens have evolved various mechanisms to inhibit or evade the activation of inflammasomes. Therefore, we review the interactions between viruses and microbes with inflammasomes during the invasion process, highlight the molecular mechanisms of inflammasome activation induced by microbial pathogen infection, and highlight the corresponding strategies that pathogens employ to evade inflammasome activity. Finally, we also discuss potential therapeutic strategies for the treatment of pathogenic microbial infections via the targeting of inflammasomes and their products.
    Keywords:  AIM2; Evasion; Inflammasome; Microbe; NLRP3; Viral
    DOI:  https://doi.org/10.1007/s00018-025-05575-2
  2. Parasitol Res. 2025 Jan 20. 124(1): 9
    Activation of the COX-2/mPGES-1/PGE-2 cascade through the NLRP3 inflammasome contributes to Angiostrongylus cantonensis-induced eosinophilic meningoencephalitis.
    Ke-Min Chen, Cheng-You Lu, Shih-Chan Lai.
      Prostaglandin E2 (PGE-2) is synthesised by cyclooxygenase-2 (COX-2) and microsomal prostaglandin E synthase 1 (mPGES-1). PGE-2 exhibits pro-inflammatory properties in inflammatory conditions. However, there remains limited understanding of the COX-2/mPGES-1/PGE-2 pathway in Angiostrongylus cantonensis-induced meningoencephalitis. This study revealed several key findings regarding the activation of the COX-2/mPGES-1/PGE-2 pathway and its correlation with eosinophilic meningoencephalitis induced by A. cantonensis infection. Immunostaining revealed an increase in the expression of COX-2 and mPGES-1 in the subarachnoid space and glial cells compared to control subjects. Inhibition of the NLRP3 inflammasome by small interfering RNA (siRNA) blocked extracellular secretory proteins (ESPs) stimulated COX-2, mPGES-1 and PGE-2 in microglia. MCC950, an NLRP3 inhibitor, inhibited the levels of the COX-2, mPGES-1, and PGE-2 proteins induced by A. cantonensis in mice. Treatment of mice infected with A. cantonensis with the COX-2 inhibitor NS398 significantly reduced the levels of mPGES-1, PGE-2, and matrix metalloproteinase-9 (MMP-9) levels. Similarly, the mPGES-1 inhibitor MF63 significantly reduced PGE-2 and MMP-9 levels in A. cantonensis-infected mice. Administration of MCC950, NS398, or MF63 resulted in marked attenuation of blood-brain barrier (BBB) permeability and eosinophil counts in A. cantonensis-infected mice. These findings highlight the critical role of the COX-2/mPGES-1/PGE-2 pathway and its regulation by the NLRP3 inflammasome in the pathogenesis of eosinophilic meningoencephalitis induced by A. cantonensis infection. Furthermore, pharmacological interventions targeting this pathway, such as MCC950, NS398, and MF63, show promising therapeutic potential in mitigating associated inflammatory responses and disruption of the BBB. The results indicate that blocking NLRP3 using pharmacological (MCC950) and gene silencing (siNLRP3) methods emphasised the crucial involvement of NLRP3 in the COX-2/mPGES-1/PGE-2 pathway. This suggests that the activation of the COX-2/mPGES-1/PGE-2 axis in response to A. cantonensis infection may be mediated through a mechanism involving the NLRP3 inflammasome.
    Keywords:   Angiostrongylus cantonensis ; Cyclooxygenase-2; Inflammasome; Meningoencephalitis; Prostaglandin E2
    DOI:  https://doi.org/10.1007/s00436-025-08454-8
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