Vi capsular polysaccharide of Salmonella enterica serovar Typhi disturbs autophagy to increase intracellular survival in macrophages.

The autophagy pathway plays a crucial role in resistance to bacterial infection in the host. Salmonella enterica serovar Typhi (S. Typhi), a human restricted pathogen, causes a systemic infection known as typhoid fever. Vi capsular polysaccharide not only forms a physical barrier on the surface of S. Typhi but also serves as an important virulence factor. Here, the effects of Vi expression on autophagy of host cells was investigated. Vi was highly expressed in super optimal broth (SOB) medium for 8 h and in the early stage of macrophage infection. Strains of S. Typhi with a mutation in Vi capsule, ΔtviA and ΔvexE, were constructed and showed lower intracellular survival in macrophage THP-1 cells compared with wild type strain. Western blot, immunofluorescence and flow cytometry were used to detected the autophagy level of macrophages infected by Vi mutant and wild type strains, respectively. Autophagy receptor p62 protein level significantly decreased and LC3-II protein level significantly increased in Vi mutant strains compared with wild type strain, which indicated increased autophagy in macrophages infected by Vi mutant strains. The qRT-PCR and western blot results showed that not Nod1, but Nod2 and Galectin-8 were up-regulated in Vi mutant strains. In summary, we propose that Vi capsule of S. Typhi decreased autophagy of macrophages to increase its survival in host cells by decreasing the expression of Nod2 and Galectin-8.