Role of Tissue-Specific Factors in the Control of Immunity

National Institute Of Allergy And Infectious Diseases

Investigators

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Abstract

Maintenance of tolerance and restoration of host homeostasis following insults relies on a complex and coordinated set of innate and adaptive responses. These tissue tailored responses are controlled by specialized populations of cells that integrate local cues such as defined metabolites or cytokines in order to induce responses in a way that preserve the functional requirements of each tissue. Our work helped to identify some of these tissue specific immunological networks and their role in the development of appropriate and controlled immune responses. More particularly we identified novel mechanisms of regulation in the gastrointestinal tract involving a dialogue between ILC and antigen presenting cells. Our findings also reveal that, following GI infection, control of commensal outgrowth is a highly coordinated process involving both the host response and microbial signals. Notably, emigration of neutrophils to the lumen results in the generation of organized intra-luminal structures that encapsulate commensals and limit their contact with the epithelium. Our data propose that the formation of luminal casts depends upon the high-affinity N-formyl peptide receptor, Fpr1. We are exploring the mechanism by which outgrowth of pathobionts is controlled during infection and the potential involvement of neutrophil extracellular trap and biofilm formation in cast formation.