Elucidating the role of the host protein, FBXO22, in the infection of macrophages with the zoonotic bacterial pathogen, Brucella.

Abstract Brucella spp. are facultative intracellular bacterial pathogens that have the ability to survive and multiply in professional nonprofessional phagocytes. Successful invasion chronic persistence indicate manipulates various host cellular processes create a replication permissive niche. The essential mechanisms factors support of remain poorly understood. RNA interference (RNAi) is potent molecular tool for understanding gene function by downregulating target expression through mRNA degradation. We used siRNA-based screening identify involved Brucella-macrophage interaction. Macrophages were treated with specific siRNAs, followed infection B. neotomae/B. melitensis quantification Brucella. identified several macrophages. Subsequently, we performed detailed characterization one proteins, FBXO22. Downregulation FBXO22 resulted diminished uptake into macrophages, which was dependent on NF-κB-mediated regulation phagocytic receptors. upregulated Brucella-infected macrophages induction receptors enhanced production pro-inflammatory cytokines NF-κB. Furthermore, found recruits effector proteins Brucella, including anti-inflammatory degradation SCF complex. Funding from Department Biotechnology (DBT) (BT/PR12301/ADV/90/176/2014)