Brucellosis is a zoonotic pathogen that causes both animal and human diseases. Brucella pathogenesis depends on the bacterial ability of inhibiting apoptosis and establishes a replicative niche inside host cells. The PI3K/Akt pathway regulates various cellular activities (cell growth, survival, and apoptosis). However, the role of the PI3K/Akt pathway in the survival of 16M in RAW264.7 macrophages remains largely unknown. In our report, we demonstrated that the PI3K/Akt pathway was activated by 16M in RAW264.7 macrophages. We found that 16M infection induced the phosphorylation of both Thr-308 and Ser-473 of Akt in a time-dependent manner. This phosphorylation was inhibited by LY in a dose-dependent manner. Inhibition of PI3K/Akt with LY significantly reduced the internalisation and replication of 16M and induced 16M-dependent inhibition of apoptosis, and induced Th1 and proinflammatory responses both in vitro and in vivo and protected mice against 16M infection. These results indicated that the PI3K/Akt pathway plays an important role in 16M survival both in vitro and in vivo, which will help to unravel the pathogenic mechanisms of 16M.

Key words: Brucella melitensis 16M, Cell apoptosis, PI3K/Akt pathway, Survival