Arginase 1 (ARG1) is a cytosolic
enzyme that cleaves
L-arginine, the substrate of
inducible nitric oxide synthase (iNOS), and thereby impairs the control of various intracellular pathogens. Herein, we investigated the role of ARG1 during
infection with Salmonella enterica serovar Typhimurium (S.tm). To study the impact of ARG1 on
Salmonella infections in vitro, bone marrow-derived macrophages (BMDM) from C57BL/6N wild-type, ARG1-deficient Tie2Cre+/-ARG1fl/fl and NRAMPG169 C57BL/6N mice were infected with S.tm. In wild-type BMDM, ARG1 was induced by S.tm and further upregulated by the addition of
interleukin (IL)-4, whereas
interferon-γ had an inhibitory effect. Deletion of ARG1 did not result in a reduction in bacterial numbers. In vivo, Arg1
mRNA was upregulated in the spleen, but not in the liver of C57BL/6N mice following intraperitoneal S.tm
infection. The genetic deletion of ARG1 (Tie2Cre+/-ARG1fl/fl) or its pharmacological inhibition with
CB-1158 neither affected the numbers of S.tm in spleen, liver and blood nor the expression of host response genes such as iNOS,
IL-6 or tumour
necrosis factor (TNF). Furthermore, ARG1 was dispensable for pathogen control irrespective of the presence or absence of the phagolysosomal
natural resistance-associated macrophage protein 1 (NRAMP1). Thus, unlike the detrimental function of ARG1 seen during
infections with other intraphagosomal microorganisms, ARG1 did not support bacterial survival in systemic
salmonellosis, indicating differential roles of
arginine metabolism for host immune response and microbe persistence depending on the type of pathogen.