Sweet and sour: Uncovering bacterial antigen biosynthesis and the mechanism of host protection by iNKT cells

• Applicant: Dr. Nadine Hartmann
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens ; Immunology
• Term: from 2014 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 270440647

Invariant natural killer T (iNKT) cells are a versatile population of T lymphocytes that bridge the innate and adaptive immune responses. A unique characteristic of iNKT cells is their semi-invariant T cell antigen receptor, which recognizes microbial glycolipids presented by CD1d. Following activation by antigens, iNKT cells rapidly secrete cytokines. Thus, they are involved in immune and inflammatory responses as well as in anti-tumor reactions. Furthermore, iNKT cells play a crucial role in host defense against pathogens like Streptococcus pneumoniae, which is a causal agent of pneumonia leading to serious diseases and deaths in young children worldwide. Although some antigens that activate iNKT cells from microbial pathogens have already been identified, the biosynthetic pathway of those antigens and the mode of iNKT cell activation are still poorly understood. Within the DFG Research Fellowship, I propose to generate bacterial mutants with a loss or alteration in their antigenic content, focusing on S. pneumoniae, and to study those mutants for their lipidome content and their ability to activate iNKT cells. Thus, I aim to discover the relation between the bacterial lipid metabolism, the antigenic content of the bacteria and the mode of iNKT cell stimulation. In addition to foreign antigen recognition, iNKT cells can also be activated by other means, including responses to self-antigens and the presence of inflammatory cytokines, such as interleukin-12 and interleukin-18. The mutants will allow me to dissect the relative importance of these activation pathways in vivo. A better understanding of the means to stimulate iNKT cells could be a powerful tool in the fight against clinically important pathogens. However, the exact mechanism of host protection still needs to be elucidated. Therefore I propose to study and identify the cytokine repertoire that is crucial for host defense to uncover the mechanism of iNKT cell protective responses in the lung.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Mitchell Kronenberg, Ph.D.