Salmonella Typhi is the causative agent of typhoid fever, which is a life-threatening, systemic disease, with an estimated global disease burden of 21.6 million cases annually, resulting in about 220,000 deaths. Due to the absence of convenient animals models to study S. Typhi and other typhoidal Salmonella serovars, our understanding of typhoid fever pathogenesis is still incomplete.
Like other Salmonella serovars, S. Typhi is phagocytosed by host macrophages and survives and replicates intracellularly within these macrophages. Interestingly, one important virulence factor of S. Typhi is the polysaccharide capsular antigen Vi, which, like many of the bacterial capsules produced by extracellular bacteria, has long been thought to play a role in preventing phagocytosis and complement killing of S. Typhi.
Thus, we encounter a paradox in which a bacteria that survives and replicates within macrophages as part of its life cycle, also possesses an anti-phagocytic capsule, which is more characteristic of an extracellular pathogen.
Here, we demonstrate that the S. Typhi Vi capsule selectively prevents or allows phagocytosis and uptake of the bacteria depending on the host cell type. The Vi capsule prevents phagocytosis by neutrophils, but does not prevent uptake of the bacteria by macrophages.
Instead, we propose that macrophages possess cell surface receptors that specifically bind to and recognize polysaccharides present in the Vi capsule, thereby facilitating engulfment.
