Inhibitory leukocyte immunoglobulin-like receptors (LILRs) in bacterial infection biology

Innate immune responses are tightly regulated to protect the host from invading bacteria without inducing detrimental inflammation and tissue damage. Inhibitory receptors of the leukocyte immunoglobulin-like receptors (LILRs) family are expressed by human innate immune cells and are negative regulators of their activation and immune responses. Thus, the inhibitory LILRs are proposed to have a critical role in orchestrating immunity and resolving inflammation. However, whether these receptors have a role during invasive bacterial infections remains elusive. In this grant, we will test the hypothesis that bacterial pathogens have evolved sophisticated mechanisms to interact with inhibitory LILRs to suppress innate immune responses for immune evasion and to promote infection. The key goals are to 1) analyse the structure-function relationship of bacterial ligand and inhibitory LILR interactions, 2) measure the capacity of bacteria-inhibitory LILR interactions to suppress antibacterial responses, 3) assess if these interactions promote bacterial infection, and 4) characterise how LILR variation impacts ligand recognition and antibacterial responses. Using bacteriological-, biochemical-, cell- and in vivo- approaches to address these goals, the project will lead to a significant shift in our understanding of how inhibitory LILRs regulate infection and uncover the therapeutic potential of targeting inhibitory LILR- ligand interactions in future antibacterial therapeutics.