Intracellular complement protein C3 promotes cell survival via Factor B (FB).

Abstract Intracellular complement proteins such as C3 and FB play protective role during stress-induced cell death. C3−/−and Cfb−/−mice had worse Pseudomonas aeruginosa (P.a.)-induced acute lung injury at 24 h post infection compared to wildtype (WT) mice. However, the mechanism by which exerts these functions is unclear. We performed CRISPR-induced deletion of C3and CFBin BEAS-2B cells, a human tracheobronchial airway epithelial line assessed key findings in primary cells. also tested our observations bone-marrow derived macrophages (BMDM) from Cfb−/−versus WT Measures were quantified C3−/−, Cfb−/−and mice infected with PA57, clinical P.a.strain. observed that FB-deficient cells have increased death overtime their parent clones setting both oxidative stress P.a.infection vitro. An autophagic response, along apoptosis, was deficiency. On further evaluation, deficiency resulted significantly lower AKT-mTOR signaling P.a.infection. phospho-P70 S6 kinase levels, higher LC3-II levels A similar phenotype BMDMs Cfb−/−compared Cfb−/−mouse intracellular bacterial burden FB-sufficient controls, suggesting lack altered processing P.a. The effect present even when its secretion inhibited but abolished conclude protein plays an essential survival via FB.