The inflammasomes: crosstalk between innate immunity and hematology

Dutra, Valéria de Freitas; Leal, Vinícius Nunes Cordeiro; Pontillo, Alessandra

doi:10.1007/s00011-022-01646-3

Cited by 2 publications

(1 citation statement)

References 112 publications

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“…It consists of three parts: the NLRP3 sensor protein (nucleotide-binding domain (NBD)-containing protein and leucine-rich repeat (LRR)-containing protein), the ASC adaptor protein (apoptotic speck protein containing a caspase recruitment domain), and the caspase-1 effector protein [ 10 , 11 , 12 ]. NLRP3 has been detected in myeloid immune cells like neutrophils, monocytes, and dendritic cells and can be activated by microbial infections, endogenous damage signals, and pore-forming toxins [ 13 , 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Bovine DDX3X Restrains Bovine SP110c-Mediated Activation of Inflammasome in Macrophages

Li,

Han,

Jing

et al. 2024

Animals

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The inflammasome is a vital part of the host’s innate immunity activated by cellular infection or stress. Our previous research identified the bovine SP110c isoform (bSP110c) as a novel activator of the inflammasome that promoted the secretion of proinflammatory cytokines IL-1β and IL-18 in macrophages infected with Listeria monocytogenes or stimulated with lipopolysaccharide (LPS). However, the exact molecular mechanism for inhibiting bSP110c-induced inflammasome activation requires further clarification. Here, the researchers identified bovine DDX3X (bDDX3X) as an NLRP3-associated protein and an inhibitor of the bSP110c-induced inflammasome in the human THP1 macrophage cell line. Immunoprecipitation showed that bDDX3X interacted with the bSP110c CARD domain via its helicase domain. The co-expression of bSP110c and bDDX3X in THP1 macrophages significantly prevented the bSP110c-induced activation of inflammasomes. In addition, both bDDX3X and bSP110c interacted with bovine NLRP3 (bNLRP3), and bDDX3X enhanced the interaction between bSP110c and bNLRP3. The expression of bDDX3X in nigericin-stimulated THP1 macrophages significantly suppressed NLRP3 inflammasome activation, ASC speck formation, and pyroptosis. These findings demonstrate that bDDX3X negatively regulates the bSP110c-mediated inflammatory response by restricting the activation of the NLRP3 inflammasome. This discovery unveils a novel regulatory mechanism involving bDDX3X and bSP110c in coordinating inflammasome activation and subsequent cell-fate decisions in LPS-treated macrophages and, in turn, constitutes a step forward toward the implementation of marker-assisted selection in breeding programs aimed at utilizing cattle’s immune defenses.

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