Arginine transport is impaired in C57Bl/6 mouse macrophages as a result of a deletion in the promoter of slc7a2 (CAT2) and Leishmania infection is reduced

Abstract

Host genetic factors play a crucial role in immune response. To determine whether the differences betweenC57Bl/6 and BALB-C mice are due only to the production of cytokines by T-helper 1 cells or T-helper 2 cells,we obtained bone marrow–derived macrophages from both strains and incubated them with these cytokines.Although the induction of Nos2 and Arg1 was similar in the 2 strains, infectivity to <em>Leishmania major</em> differed,as did macrophage uptake of arginine, which was higher in BALB-C macrophages. The levels of interferon γ–and interleukin 4–dependent induction of the cationic amino acid transporter SLC7A2 (also known as “cationicamino acid transporter 2,” or “CAT2”) were decreased in macrophages from C57Bl/6 mice. This reductionwas a result of a deletion in the promoter of one of the 4 AGGG repeats. These results demonstrate that theavailability of arginine controls critical aspects of macrophage activation and reveal a factor for susceptibility to Leishmania infection.