Absence of the fatty acid binding protein5 (FABP5) inhibits the establishment of resident memory T cells after a secondary Listeria monocytogenes infection

Abstract

Abstract Fatty acid binding protein 5 (FABP5) is a member of the family of fatty acid binding proteins involved in fatty acid uptake, transport, and metabolism. FABP5 is ubiquitously expressed, including in T cells. During the course of an immune reaction, T cells undergo multiple changes to their metabolism. Once naïve T cells are activated, expansion is triggered, and cells differentiate to become effector cells accompanied by a metabolic change from fatty acid oxidation to glycolysis. Once the pathogen is eliminated, effector cells differentiate into memory cells, with central memory (TCM) and effector memory (TEM) cells surveying the circulation and resident memory (TRM) cells establishing a tissue memory pool that can quickly react to localized reinfection. These TRM cells are thought to rely on lipid uptake and fatty acid oxidation for survival. We wanted to investigate the effect of FABP5 on the development of CD8+ TRM cells in the context of a Listeria monocytogenes (Lm) infection. We had previously shown that the lack of FABP5 leads to a resistance to Lm in mice after a single infection, while the overexpression of FABP5 showed increased mortality and bacterial burden. Here, we used WT and FABP5−/− mice in an infection model with Lm-Ova to analyze the innate and antigen-specific adaptive immune responses. To this end, WT and FABP5−/− mice were infected i.v. with Lm-Ova and their immune responses analyzed at various days after. We show that while the primary immune response is improved in FABP5−/−, there was a profound negative effect on the secondary response. This was based on a severe reduction of Ova-specific TRM in the liver while TCM and TEM populations were unaffected. Flow analyses and functional assays taken throughout will be presented. Supported by NHlDI 1R01HL141264 Supported by NHlDI 1R01HL141264