Research in the van der Velden laboratory has been focused on host interactions with Salmonella, with an emphasis on the immunology of infection. The goal of our research is to elucidate mechanisms that control the balance between the pathogen, the host, and its gut microbiota. Our research can be divided into the following two thematic projects:

1. Role of inflammatory monocytes in immunity and host defense against Salmonella.

Salmonella exploit gut inflammation to edge out competing microbes in the intestinal lumen and establish infection; yet, how Salmonella achieve this feat is not well understood. We have published that inflammatory monocytes promote nitrate-dependent Salmonella expansion in the lumen of the inflamed intestine, indicating that Salmonella exploit these innate immune cells to establish infection and promote disease progression. A current project in the laboratory continues to explore the role of inflammatory monocytes in the pathogenesis of Salmonella-induced colitis.

As part of a related project, we have published that inflammatory monocytes exhibit both protective and immunosuppressive properties that may influence the outcome of persistent Salmonella infection. A current project in the laboratory continues to explore the role of inflammatory monocytes in the pathogenesis of persistent Salmonella infection.

2. Inhibition of T cells by Salmonella.

T cells play an essential role in Salmonella clearance; yet, T cell responses to Salmonella are dampened during infection by mechanisms that are not well understood. We have published that an asparagine hydrolase produced by Salmonella inhibits T cell responses and mediates virulence. In addition, we have published that asparagine deprivation such as that mediated by the asparagine hydrolase of Salmonella causes suppression of activation-induced T cell metabolic reprogramming. Most recently, we have published that asparagine catabolism contributes to Salmonella virulence, further indicating that the competition for nutritional asparagine is a key battle at the host-pathogen interface. A current project in the laboratory continues to explore the role of asparagine metabolism in the pathogenesis of and host response to bacterial infection.