MAIT cells in a human model of <em>Salmonella </em>Paratyphi infection — ASN Events

MAIT cells in a human model of Salmonella Paratyphi infection (#104)

Lauren J Howson , Giorgio Napolitani 1 , Hemza Ghadbane 1 , Prathiba Kurupati 1 , Dawn Shepherd 1 , Mariolina Salio 1 , Andrew J Pollard 2 , Vincenzo Cerundolo 1
  1. MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom
  2. Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Oxford, United Kingdom

The role of MAIT cells in responding to bacterially infected cells has been well characterised. A less explored area of research is the dynamics of MAIT cell responses in the host during human bacterial infections. To explore this, we used samples from a trial where healthy adult volunteers are recruited and infected with Salmonella enterica serovarParatyphi A and blood samples are taken at regular intervals during the course of infection.

Volunteers are tested for S. Paratyphipresent in the blood during the first two weeks and if they develop fever or bacteraemia they are diagnosed with systemic infection and treated with antibiotics. Asymptomatic individuals are treated with antibiotics after two weeks.

Our results demonstrate that during the first two weeks from challenge with S. Paratyphi, MAIT cells became activated in individuals diagnosed with systemic infection and a larger proportion of MAIT cells were reactive to S. Paratyphiboth during and after infection. Further analysis of the TCR repertoire of circulating MAIT cells during the course of the infection revealed the preferential expansion of defined MAIT cell clones in response to infection.

Our results indicate that MAIT cells may play a role in human S. Paratyphi infection and suggest the presence of immunodominant MAIT cell clones during the infection. Ongoing experiments will aim to characterise and compare TCR usage and phenotype of circulating and gut mucosa resident MAIT cells during S. Paratyphi infection.