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Diverse autoinhibitory mechanisms of FIIND-containing proteins: Insight into regulation of NLRP1 and CARD8 inflammasome.
PLoS Pathog
January 2025
Institute of Pediatric Infection, Immunity, and Critical Care Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Function-to-find domain (FIIND)-containing proteins, including NLRP1 and CARD8, are vital components of the inflammasome signaling pathway, critical for the innate immune response. These proteins exist in various forms due to autoproteolysis within the FIIND domain, resulting in full-length (FL), cleaved N-terminal (NT), and cleaved C-terminal (CT) peptides, which form autoinhibitory complexes in the steady state. However, the detailed mechanism remains elusive.
View Article and Find Full Text PDFCo-option of mitochondrial nucleic acid-sensing pathways by HSV-1 UL12.5 for reactivation from latent infection.
Proc Natl Acad Sci U S A
January 2025
Department of Microbiology, Immunology and Cancer Biology, University of Virginia, Charlottesville, VA 22908.
Although viruses subvert innate immune pathways for their replication, there is evidence they can also co-opt antiviral responses for their benefit. The ubiquitous human pathogen, Herpes simplex virus-1 (HSV-1), encodes a protein (UL12.5) that induces the release of mitochondrial nucleic acid into the cytosol, which activates immune-sensing pathways and reduces productive replication in nonneuronal cells.
View Article and Find Full Text PDFAssociations between the gut microbiome, inflammation and cardiovascular profiles in people with HIV.
J Infect Dis
January 2025
School of Medicine, University College Dublin, Belfield, Dublin 4, Ireland.
Background: Inflammation and innate immune activation are associated with chronic HIV infection, despite effective treatment. Although gut microbiota alterations are linked to systemic inflammation, the relationships between the gut microbiome, inflammation and HIV remain unclear.
Methods: The UPBEAT-CAD sub-study, examining cardiovascular disease (CVD) risk in HIV, enrolled participants matched on HIV status and traditional CVD risk factors.
The Innate Immune Sensor Zbp1 Mediates Central Nervous System Inflammation Induced by Angiostrongylus Cantonensis by Promoting Macrophage Inflammatory Phenotypes.
Adv Sci (Weinh)
January 2025
Key Laboratory of Tropical Disease Control (Sun Yat-Sen University), Ministry of Education, Guangzhou, Guangdong, 510080, China.
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 of eosinophils, myeloid cells, macrophages, neutrophils, and Ly6C monocytes is observed in the brains of AC-infected mice, with macrophages being the most abundant.
View Article and Find Full Text PDFTLR4 Inhibition Attenuated LPS-Induced Proinflammatory Signaling and Cytokine Release in Mouse Hearts and Cardiomyocytes.
Immun Inflamm Dis
January 2025
Division of Physiology, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
Background: Sepsis is associated with myocardial injury and early mortality. The innate immune receptor Toll-like receptor 4 (TLR4) can recognize pathogen-associated-molecular-patterns (PAMPs) and damage-associated molecular patterns (DAMPs); the latter are released during tissue injury. We hypothesized that TLR4 inhibition reduces proinflammatory signaling and cytokine release in: (1) LPS or Escherichia coli-treated isolated mouse heart; (2) LPS-treated mouse primary adult cardiomyocytes; and (3) the isolated heart during ischemia-reperfusion.
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