Arginine transport is impaired in C57Bl/6 mouse macrophages as a result of a deletion in the promoter of Slc7a2 (CAT2), and susceptibility to Leishmania infection is reduced

J Infect Dis. 2013 Jun 1;207(11):1684-93. doi: 10.1093/infdis/jit084. Epub 2013 Mar 4.

Abstract

Host genetic factors play a crucial role in immune response. To determine whether the differences between C57Bl/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 Leishmania major 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 "cationic amino acid transporter 2," or "CAT2") were decreased in macrophages from C57Bl/6 mice. This reduction was a result of a deletion in the promoter of one of the 4 AGGG repeats. These results demonstrate that the availability of arginine controls critical aspects of macrophage activation and reveal a factor for susceptibility to Leishmania infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Transport Systems, Basic / genetics*
  • Animals
  • Arginine / metabolism*
  • Biological Transport
  • Cells, Cultured
  • Disease Resistance*
  • Leishmania major / immunology*
  • Leishmaniasis / genetics*
  • Macrophages / metabolism*
  • Macrophages / parasitology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Promoter Regions, Genetic
  • Sequence Deletion*

Substances

  • Amino Acid Transport Systems, Basic
  • Slc7a2 protein, mouse
  • Arginine