biostudies-literatureTsai CMNHLBI NIH HHSNIGMS NIH HHS333-343https://www.ebi.ac.uk/biostudies/studies/S-EPMC7383293biostudies-literatureUnknown12(4)Pathogenic microorganisms are sensed by the inflammasome, resulting in the release of the pro-immune and proinflammatory cytokine interleukin-1β (IL-1β). In humans, the paired <underline>s</underline>ialic acid-binding Ig-like lectin receptors Siglec-5 (inhibitory) and Siglec-14 (activating) have been shown to have reciprocal roles in regulating macrophage immune responses, but their interaction with IL-1β signaling and the inflammasome has not been characterized. Here we show that in response to known inflammasome activators (ATP, nigericin) or the sialic acid-expressing human bacterial pathogen group B Streptococcus (GBS), the presence of Siglec-14 enhances, whereas Siglec-5 reduces, inflammasome activation and macrophage IL-1β release. Human THP-1 macrophages stably transfected with SigJournal of innate immunitySiglec-14 Enhances NLRP3-Inflammasome Activation in Macrophages.PMC7383293K12 GM068524P01 HL107150Varki AFong JJLiu JZHughes GTsai CMAli SRNizet VRiestra AMfalseSiglec-14 Enhances NLRP3-Inflammasome Activation in Macrophages.Pathogenic microorganisms are sensed by the inflammasome, resulting in the release of the pro-immune and proinflammatory cytokine interleukin-1β (IL-1β). In humans, the paired <underline>s</underline>ialic acid-binding Ig-like lectin receptors Siglec-5 (inhibitory) and Siglec-14 (activating) have been shown to have reciprocal roles in regulating macrophage immune responses, but their interaction with IL-1β signaling and the inflammasome has not been characterized. Here we show that in response to known inflammasome activators (ATP, nigericin) or the sialic acid-expressing human bacterial pathogen group B Streptococcus (GBS), the presence of Siglec-14 enhances, whereas Siglec-5 reduces, inflammasome activation and macrophage IL-1β release. Human THP-1 macrophages stably transfected with Sig2020-01-01T00:00:00Z20202025-04-04T07:40:33.17Z2025-04-04T07:40:33.17ZS-EPMC73832933180555210.1159/000504323