12 research outputs found
Human IRF1 governs macrophagic IFN-Îł immunity to mycobacteria
Inborn errors of human IFN-Îł-dependent macrophagic immunity underlie mycobacterial diseases, whereas inborn errors of IFN-α/ÎČ-dependent intrinsic immunity underlie viral diseases. Both types of IFNs induce the transcription factor IRF1. We describe unrelated children with inherited complete IRF1 deficiency and early-onset, multiple, life-threatening diseases caused by weakly virulent mycobacteria and related intramacrophagic pathogens. These children have no history of severe viral disease, despite exposure to many viruses, including SARS-CoV-2, which is life-threatening in individuals with impaired IFN-α/ÎČ immunity. In leukocytes or fibroblasts stimulated in vitro, IRF1-dependent responses to IFN-Îł are, both quantitatively and qualitatively, much stronger than those to IFN-α/ÎČ. Moreover, IRF1-deficient mononuclear phagocytes do not control mycobacteria and related pathogens normally when stimulated with IFN-Îł. By contrast, IFN-α/ÎČ-dependent intrinsic immunity to nine viruses, including SARS-CoV-2, is almost normal in IRF1-deficient fibroblasts. Human IRF1 is essential for IFN-Îł-dependent macrophagic immunity to mycobacteria, but largely redundant for IFN-α/ÎČ-dependent antiviral immunity
O mundo antigo visto por lentes contemporĂąneas: as extremas direitas na França nas dĂ©cadas de 1980 e 90, ou da instrumentalidade da AntigĂŒidade
What do they talk about when they talk about Europe? Euro-ambivalence in far right ideology
Human IRF1 governs macrophagic IFN-Îł immunity to mycobacteria
International audienceHighlights d Inherited complete human IRF1 deficiency underlies severe mycobacterial disease d Human IRF1 is essential for IFN-g-dependent macrophagic immunity to mycobacteria d Human IRF1 is essential for IFN-g-and STAT1-dependent immunity to mycobacteria d Human IRF1 is largely redundant for IFN-a/b-dependent antiviral intrinsic immunity Authors Je ÂŽre ÂŽmie Rosain
Randomised, controlled trial of avocadoâsoybean unsaponifiable (Piascledine) effect on structure modification in hip osteoarthritis: the ERADIAS study
Inborn errors of OAS-RNase L in SARS-CoV-2-related multisystem inflammatory syndrome in children
Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of OAS1, OAS2, or RNASEL in five unrelated children with MIS-C. The cytosolic double-stranded RNA (dsRNA)-sensing OAS1 and OAS2 generate 2'-5'-linked oligoadenylates (2-5A) that activate the single-stranded RNA-degrading ribonuclease L (RNase L). Monocytic cell lines and primary myeloid cells with OAS1, OAS2, or RNase L deficiencies produce excessive amounts of inflammatory cytokines upon dsRNA or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stimulation. Exogenous 2-5A suppresses cytokine production in OAS1-deficient but not RNase L-deficient cells. Cytokine production in RNase L-deficient cells is impaired by MDA5 or RIG-I deficiency and abolished by mitochondrial antiviral-signaling protein (MAVS) deficiency. Recessive OAS-RNase L deficiencies in these patients unleash the production of SARS-CoV-2-triggered, MAVS-mediated inflammatory cytokines by mononuclear phagocytes, thereby underlying MIS-C