1/ Today in @ScienceMagazine, @aspaan1 & colleagues show that human #OTULIN #haploinsufficiency impairs non-leukocytic cell-intrinsic immunity to the #staphylococcal alpha-toxin (science.org/doi/10.1126/sc…).
2/ They discovered OTULIN haploinsufficiency via a genome-wide approach in a cohort of patients with unexplained, life-threatening staphylococcal disease – the findings are relevant in vivo. 
3/ The clinical hallmark of OTULIN haploinsufficiency is necrosis of the skin and/or lungs, typically triggered by infections with #Staphylococcus aureus.
4/ OTULIN haploinsufficiency is related to but different from autosomal recessive OTULIN deficiency (pnas.org/doi/full/10.10…), which is a purely auto-inflammatory condition (doi.org/10.1016/j.cell…).
5/ Most patients with cri-du-chat syndrome, also known as 5p- syndrome, lack OTULIN, explaining their infections (link.springer.com/article/10.100…). A rare inborn error of immunity helps understanding a more common chromosomal anomaly.
6/ Naturally elicited antibodies against alpha-toxin can compensate for OTULIN haploinsufficiency, reminiscent of LTA-specific Abs in patients with TIRAP deficiency (doi.org/10.1016/j.cell…), and explain in part incomplete clinical penetrance.
7/ OTULIN haploinsufficiency is the first defect of non-hematopoietic cell-intrinsic immunity to a bacterial infection in humans. Multiple examples have been previously documented for immunity to viruses (doi.org/10.1126/scienc…).
8/ Thank you to coauthors of @aspaan1, namely @ALNeehus, @frapaport, @Keenan__Lacey, @davidhum8, @MelanieMigaud, @Tatianakochetk1, @HeesterbeekDani, @AshleyDuMontPhD, @SolenneChardon1, @TimourBaslan, @zhangpeng1202, @ryangrui, @BogunovicLab, @StanLyonnet, @ldnotar, @ErdalSag…
9/ @BenedicteNeven, @IsabelleMeyts, @RikSchrijvers, @anne_puel, @BustamanteJaci1, @TorresVJ_Lab, @LabListon, @LaurentAbel4, @Boisson_Bebo and others not yet on Twitter!
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