Welcome to the Laboratory of Stephen Mcsorley


We study the innate and adaptive immune response to Salmonella and Chlamydia infection and are particularly interested in visualizing these responses in mucosal tissues.

Salmonella are a common source of food-borne infection and commonly cause local gastrointestinal disease in the US and other developed nations. However, in developing nations, Salmonella can also cause serious disseminated infections and effective vaccines are urgently needed. Salmonella serovar Typhi causes typhoid fever, which kills over 200,000 people every year, and is a particularly serious infection of young children. Salmonella serovar Typhimurium is one of several serovars that causes disseminated bacteremia in young children or people suffering from HIV or malaria. The immunology of these infections is poorly understood, limiting the potential for new vaccines for these diseases.


One aim of our laboratory is to develop better immunological tools that allow detailed study of CD4 T cell and antibody responses to Salmonella. So far, we have generated the only Salmonella-specific TCR transgenic mouse and MHC class-II tetramers and these reagents allow us to identify Salmonella-specific immune cells as they respond to oral infection or vaccination. We continue to refine and develop new reagents to expand our understanding of immunity to Salmonella. We have recently expanded this approach to examining immune responses to vaginal infection with Chlamydia infection. This allows us to compare and contrast the immune response to two bacterial infections that differentially affect the intestinal and genital mucosa.

Figure 1. Click image to zoom

We are also actively engaged in the identification of the antigenic targets of the Salmonella-specific immune response. This allows us to develop better immunological reagents but also allows us to determine whether proteins from Salmonella can be used as sub-unit vaccines.

We are also interested in characterizing the innate immune response to bacterial infection. Innate immune responses are initiated rapidly after infection and commonly rely on innate immune receptors that recognize common bacteria structures. We are particularly focused on the recognition of bacterial flagellin by Toll-like Receptor 5 (TLR5), an innate immune receptor found in mice and humans. We have recently found that TLR5 recognition of Salmonella flagellin directs the subsequent adaptive immune response to this same antigen. We are currently following up on this finding by trying to identify the intracellular signaling pathway involved in this process.

Figure 2. Click image to zoom

Lastly, we are interested in how antibiotic treatment of typhoid affects the immune response to Salmonella. We have found that intervention with antibiotics adversely affects immunity and may explain why people living in endemic areas suffer from repeated infection. We have also developed the first model of relapsing Salmonella infection that should allow greater understanding of why some patients harbor persistent bacteria that cause repeated infections.

Figure 3. Click image to zoom



 



Stephen J. McSorley, PhD
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