Domain-specific role of IL-17RA in controlling Klebsiella pneumoniae lung infection

ABSTRACT IL-17 is an essential mediator of immunity to Klebsiella pneumoniae (KP). Animal models lacking IL-17 signaling or having IL-17 receptor (IL-17R) deficiency are susceptible to KP pneumonia. Although considerable research effort has focused on how Th17 cells are generated and regulated, the mechanisms by which IL-17 and its receptor IL-17R mediate specific downstream signals in relevant disease processes such as KP pneumonia are not fully elucidated. Our efforts to understand KP pneumonia in mouse models revealed that the distal domain of IL-17RA, also known as CBAD, is indispensable to control this infection. Thus, we propose to determine the immune and molecular mechanisms by which the IL-17RA CBAD domain constrains KP pneumonia. We will also perform parallel analyses to evaluate the cell-type-specific response by single-cell RNASeq. The findings generated from this proposal will help us understand IL-17- dependent signaling mechanism by which KP pneumonia can be controlled and to evaluate the lung immune response at a single cell resolution.