(A) Fibroblasts from individuals acting as controls (n = 2) and patients with SLOS (n = 4) were stimulated, and media were assayed for cytokines. (B) Fibroblast IL-6 production rank ordered by clinical severity score. (C) Whole blood was LPS stimulated and assayed for cytokines (n = 7–11). (D) Peritoneal macrophages from mice of indicated genotypes were stimulated (HKLM, heat-killed L. monocytogenes) and TNF-α in media was quantified. (E–I) RAW 264.7 macrophages were treated with vehicle or BM15.766 (BM), stained with Alexa Fluor 488–cholera toxin subunit B (CtB), and imaged for (E) total intensity, (F) CtB⁺ foci/cell, and (G) clustering of foci. (H and I) Signal for (H) fPEG-cholesterol and (I) anti-TLR4 antibody was quantified. (J) Macrophages pretreated with vehicle/BM were LPS stimulated. MyD88 immunoprecipitates (IP) and whole cell lysates (WCL) were immunoblotted for indicated targets. (K) Bronchoalveolar lavage neutrophils (PMN) quantified 24 hours after K. pneumoniae lung infection in mice of indicated genotypes (n = 7–12). (L) qPCR for indicated targets in mouse lungs 3 days after infection with influenza A virus (n = 3–5). Data represent mean ± SEM and are representative of 2–3 independent experiments. In C and L, boxes depict the 25th–75th percentile around median; whiskers represent the minimum and maximum. ^#P = 0.05; *P < 0.05; **P < 0.01; ***P < 0.001 (unpaired 2-tailed t test for all except 1-way ANOVA with Dunnett’s post test for K).