Thioesterase PPT1 balances viral resistance and efficient T cell crosspriming in dendritic cells

We report that palmitoyl-protein thioesterase 1 (PPT1), which catabolizes lipid-modified proteins in neurons, is highly expressed in cDC1s. PPT1-deficient DCs are more susceptible to vesicular stomatitis virus (VSV) infection, and mice with PPT1 deficiency in cDC1s show impaired response to VSV. Conversely, PPT1-deficient cDC1s enhance the priming of naive CD8+ T cells into tissue-resident KLRG1+ effectors and memory T cells, resulting in rapid clearance of tumors and Listeria monocytogenes. Mechanistically, PPT1 protects steady state DCs from viruses by promoting antigen degradation and endosomal acidification via V-ATPase recruitment. After DC activation, immediate down-regulation of PPT1 is likely to facilitate efficient cross-presentation, production of costimulatory molecules and inflammatory cytokines. Thus, PPT1 acts as a molecular rheostat that allows cDC1s to crossprime efficiently without compromising viral resistance. These results suggest potential therapeutics to enhance cDC1-dependent crosspriming.

Source: The Journal of Experimental Medicine - September 1, 2019 Category: Internal Medicine Authors: Ou, P., Wen, L., Liu, X., Huang, J., Huang, X., Su, C., Wang, L., Ni, H., Reizis, B., Yang, C. Y. Tags: Innate Immunity and Inflammation, Infectious Disease and Host Defense Articles Source Type: research