Abstract

Salmonella infections have devastating effects worldwide whether they are typhoidal or non-typhoidal in origin and studying immunity to Salmonella is essential in the search for improved vaccines. Additionally, Salmonella infections are a potential paradigm for understanding intracellular infections, how T helper 1 responses develop, the induction of B cells and how bacterial components influence immunity.

In this talk I will discuss how CD4 T cell responses to Salmonella develop and are maintained. In particular I will focus on the response to the immunodominant antigen flagellin and how CD30 and OX40 are required for activated CD4 T cell survival.

In the second part of the talk I will focus on the highly atypical B cell response Salmonella induces. I will demonstrate that the resilience of this response even in the absence of CD28 or CD40L appears to be due partially to the rapid recruitment of B1b cells. Our data indicate that the outer membrane porin proteins OmpF and OmpC are targets of this B1b response. This is demonstrated by B1b induction by purified OmpF and OmpC and an abrogated induction by bacteria that lack these proteins. Furthermore transfer of B1b cells into B cell-deficient mice and vaccination could confer some protection against infection with Salmonella.

Lastly, I will briefly introduce data that query whether antibody to LPS is protective and whether CD4 T cells play a role in orchestrating protection during the early stages of secondary encounter with Salmonella.