TY - JOUR T1 - The intracellular pathogen <em>Francisella tularensis</em> escapes from adaptive immunity by metabolic adaptation JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.202201441 VL - 5 IS - 10 SP - e202201441 AU - Kensuke Shibata AU - Takashi Shimizu AU - Mashio Nakahara AU - Emi Ito AU - Francois Legoux AU - Shotaro Fujii AU - Yuka Yamada AU - Makoto Furutani-Seiki AU - Olivier Lantz AU - Sho Yamasaki AU - Masahisa Watarai AU - Mutsunori Shirai Y1 - 2022/10/01 UR - https://www.life-science-alliance.org/content/5/10/e202201441.abstract N2 - Intracellular pathogens lose many metabolic genes during their evolution from free-living bacteria, but the pathogenic consequences of their altered metabolic programs on host immunity are poorly understood. Here, we show that a pathogenic strain of Francisella tularensis subsp. tularensis (FT) has five amino acid substitutions in RibD, a converting enzyme of the riboflavin synthetic pathway responsible for generating metabolites recognized by mucosal-associated invariant T (MAIT) cells. Metabolites from a free-living strain, F. tularensis subsp. novicida (FN), activated MAIT cells in a T-cell receptor (TCR)–dependent manner, whereas introduction of FT-type ribD to the free-living strain was sufficient to attenuate this activation in both human and mouse MAIT cells. Intranasal infection in mice showed that the ribDFT-expressing FN strain induced impaired Th1-type MAIT cell expansion and resulted in reduced bacterial clearance and worsened survival compared with the wild-type free-living strain FN. These results demonstrate that F. tularensis can acquire immune evasion capacity by alteration of metabolic programs during evolution. ER -