Browsing by keyword "inflammasomes"

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    • Platelets Fuel the Inflammasome Activation of Innate Immune Cells
      Rolfes, Verena; Ribeiro, Lucas Secchim; Latz, Eicke; Arditi, Moshe; Franklin, Bernardo Simoes (2020-05-12)
      The inflammasomes control the bioactivity of pro-inflammatory cytokines of the interleukin (IL)-1 family. The inflammasome assembled by NLRP3 has been predominantly studied in homogeneous cell populations in vitro, neglecting the influence of cellular interactions that occur in vivo. Here, we show that platelets boost the inflammasome capacity of human macrophages and neutrophils and are critical for IL-1 production by monocytes. Platelets license NLRP3 transcription, thereby enhancing ASC oligomerization, caspase-1 activity, and IL-1beta secretion. Platelets influence IL-1beta production in vivo, and blood platelet counts correlate with plasmatic IL-1beta levels in malaria. Furthermore, we reveal an enriched platelet gene signature among the highest-expressed transcripts in IL-1beta-driven autoinflammatory diseases. The platelet effect is independent of cell-to-cell contact, platelet-derived lipid mediators, purines, nucleic acids, and a host of platelet cytokines, and it involves the triggering of calcium-sensing receptors on macrophages. Hence, platelets provide an additional layer of regulation of inflammasomes and IL-1-driven inflammation.

    • The PYHIN protein family as mediators of host defenses
      Schattgen, Stefan A.; Fitzgerald, Katherine A. (2011-09-01)
      The innate immune response is the first line of defense against infection and relies on the ability of immune cells to detect the presence of infection through germline-encoded pattern recognition receptors. These include the Toll-like receptors, the retinoic acid inducible gene-like receptors, the nucleotide oligomerization domain-like receptors, and a number of DNA-sensing molecules. Members of the PYHIN protein family have recently emerged as sensors of microbial DNA. PYHIN proteins bind microbial DNA and form caspase-1-activating inflammasomes (AIM2) or drive type I IFN gene transcription (IFI16). Here, we review these discoveries and highlight the emerging role of the PYHIN protein family in mammalian host defenses.