The Innate Immune Sensor Zbp1 Mediates Central Nervous System Inflammation Induced by Angiostrongylus Cantonensis by Promoting Macrophage Inflammatory Phenotypes

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 24, 2025

Abstract Angiostrongylus cantonensis (AC) is the leading cause of eosinophilic meningoencephalitis worldwide. The neuroimmune interactions between peripheral and central immune systems in angiostrongyliasis remain unclear. In this study, significant infiltration eosinophils, myeloid cells, macrophages, neutrophils, Ly6C monocytes observed brains AC‐infected mice, with macrophages being most abundant. RNA‐seq SMART‐seq analysis pattern recognition receptor (PRR) DNA sensor gene sets revealed a marked increase Z‐DNA binding protein 1 (Zbp1) expression infected mice. Confocal microscopy, RT‐qPCR, western blotting, immunohistochemistry further confirmed that Zbp1 specifically upregulated microglia. Using Zbp1‐knockout mice flow cytometry, it found knockout enhanced lymphocyte natural killer cell cytotoxicity, modulating microenvironment nervous system (CNS) during AC infection. Mechanistically, macrophage directly binds to receptor‐interacting 3 (RIP3) promote its phosphorylation, subsequently facilitating phosphorylation mixed lineage kinase domain‐like (Mlkl). activated Zbp1‐pRIP3‐pMlkl axis leads necroptosis upregulates pro‐inflammatory cytokines including TNF‐α, IL‐1α, CXCL9, CXCL10 which recruits activates cells. These findings offer new insights into pathogenic mechanisms suggest potential therapeutic strategies.

Language: Английский

Chicken C4BPM facilitates replication of H5N1 and H9N2 Avian Influenza Viruses by inhibiting the production of type I interferons

Poultry Science, Journal Year: 2025, Volume and Issue: 104(3), P. 104868 - 104868

Published: Jan. 31, 2025

Avian influenza viruses (AIVs) are potential pandemic of global concern, posing a major threat to both the poultry industry and human health. Host factors play key role in replication AIVs, while function complement component 4 binding protein, membrane (C4BPM) this process is still unclear. This research reports that C4BPM promotes H5N1 H9N2 AIVs by inhibiting type I interferons (IFNs). infection up-regulate expression chicken embryo fibroblast cells (DF-1). To verify knockout (C4BPM-KO) stable overexpressing (C4BPM-overexpressing) DF-1 were generated using lentivirus-mediated CRISPR/Cas9 gene editing technology molecular cloning strategies. Replication promoted C4BPM-overexpressing with inhibited IFNs (IFN-α, IFN-β), protein kinase R (PKR), cholesterol 25-hydroxylase (CH25H), interferon regulatory factor (IRF) 3, mitochondrial antiviral signaling (MAVS) compared cells. However, C4BPM-KO increased above related anti-viral factors. Further results showed did not affect viral adsorption, while, promote entry AIVs. These expand range host regulating suggest promising target for agent.

Language: Английский

Macrophage migration inhibitory factor facilitates replication of Senecavirus A by enhancing the glycolysis via hypoxia inducible factor 1 alpha

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 281, P. 136197 - 136197

Published: Oct. 2, 2024

Language: Английский