Title : Outer membrane protein 25 of brucella suppresses TLR-mediated expression of proinflammatory cytokines through degradation of TLRs and adaptor proteins
Toll-like receptors are essential components of innate immunity that serve as the first line of defence against invaded microorganisms. However, successful infectious pathogens subvert TLR signalling to suppress the activation of innate and adaptive responses. Brucella species are infectious intracellular bacterial pathogens causing the worldwide zoonotic disease, brucellosis that impacts the economic growth of many countries. Brucella species are considered stealthy bacterial pathogens as they efficiently evade or suppress host innate and adaptive immune responses for their chronic persistence. However, the bacterial effectors and their host targets for modulating the immune responses remain obscure. Brucella encodes various outer membrane proteins that facilitate their invasion, intracellular replication and immunomodulation. Outer membrane protein 25 of Brucellaplays an important role in immune modulation through suppression of pro-inflammatory cytokines. However, the mechanism and the signalling pathways that are targeted by Omp25 to attenuate the production of pro-inflammatory cytokines remain obscure. Here, we report that Omp25 and its variants viz.Omp25b, Omp25c and Omp25d suppress the production of proinflammatory cytokines that are mediated by various TLRs. Furthermore, we demonstrate that Omp25 and its variants promote enhanced ubiquitination and degradation of TLRs and their adaptor proteins to attenuate the expression of pro-inflammatory cytokines. Targeting multiple TLRs and adaptor proteins enables Omp25 to effectively suppress the expression of pro-inflammatory cytokines that are induced by diverse pathogen-associated molecular patterns. This can contribute to the defective adaptive immune response and the chronic persistence of Brucella in the host.
? This work can give a basic outline to study host-pathogen dynamics.
? It will help to understand the function of OMP25 of Brucella which is well-researched in areas of diagnostics and vaccine development against Brucella
? It provides insight into how gram-negative intracellular bacteria can use outer membrane proteins to modify the host response and establish a niche.
? It can help to design infection-based experiments