Salmonella Typhi survives in the host by evading a complement-dependent neutrophil immuno-surveillance (P4221)

Abstract

Abstract Vi capsular polysaccharide in S. Typhi is an important virulence factor. However, its role is incompletely understood. Previously, we have shown that the Vi capsule prevents complement component 3 mediated clearance of S. Typhi by preventing C3 fixation on the bacterial surface. Here we used isolated mouse and human neutrophils to show, at single cell level, that Vi negative S. Typhi mutant (tviB-vexE) directly triggers a chemotactic response by neutrophils when co-incubated in a medium containing autologous serum whereas Vi positive wild-type S. Typhi (Ty2) does not. Using neutrophils from C3 and C5aR deficient mice, we also show that this chemotactic response requires the complement component 5a receptor (C5aR) in neutrophils suggesting that the detection of generated C5a as a result of complement activation on the bacterial surface is a non-redundant signal used by neutrophils to move towards the bacteria. Additionally, data from our in vivo mouse model show that higher number neutrophils were associated with tviB-vexE than the WT S. Typhi an hour post interperitoneal injection of bacteria. Taken together, our data suggest that Vi capsule helps evade neutrophil detection of S. Typhi by preventing activation of C5a-dependent chemotactic response.