L-arginine and cationic amino acid transporter 2B regulate growth and survival of Leishmania amazonensis amastigotes in macrophages.
نویسندگان
چکیده
Leishmania spp. are obligate intracellular parasites, requiring a suitable microenvironment for their growth within host cells. We previously reported that the growth of Leishmania amazonensis amastigotes in murine macrophages (Mphis) was enhanced in the presence of gamma interferon (IFN-gamma), a Th1 cytokine normally associated with classical Mphi activation and killing of intracellular pathogens. In this study, we provided several lines of evidence suggesting that IFN-gamma-mediated parasite growth enhancement was associated with L-arginine transport via mouse cationic amino acid transporter 2B (mCAT-2B). (i) mRNA expression of Slc7A2, the gene encoding for mCAT-2B, as well as L-arginine transport was increased in IFN-gamma-treated Mphis. (ii) Supplementation of L-arginine in Mphi cultures increased parasite growth. (iii) Parasite growth enhancement in wild-type Mphis was inhibited in the presence of nonmetabolized L-arginine analogues. (iv) IFN-gamma-mediated parasite growth was absent in Mphis derived from mCAT-2B-deficient mice. Although we detected a clear upregulation of mCAT-2B and L-arginine transport, no measurable iNOS or arginase activities were observed in IFN-gamma-treated, infected Mphis. Together, these data suggest an involvement of a novel L-arginine usage independent of iNOS and arginase activities during IFN-gamma-mediated parasite growth enhancement. A possible role of mCAT-2B in supplying L-arginine directly to the parasites for their proliferation is discussed.
منابع مشابه
Amastigotes in Macrophages Leishmania amazonensis Survival of Transporter 2B Regulate Growth and l-Arginine and Cationic Amino Acid
متن کامل
L-arginine availability and arginase activity: Characterization of amino acid permease 3 in Leishmania amazonensis
BACKGROUND Leishmania uses the amino acid L-arginine as a substrate for arginase, enzyme that produces urea and ornithine, last precursor of polyamine pathway. This pathway is used by the parasite to replicate and it is essential to establish the infection in the mammalian host. L-arginine is not synthesized by the parasite, so its uptake occurs through the amino acid permease 3 (AAP3). AAP3 is...
متن کاملAxenic Leishmania amazonensis Promastigotes Sense both the External and Internal Arginine Pool Distinctly Regulating the Two Transporter-Coding Genes
Leishmania (L.) amazonensis uses arginine to synthesize polyamines to support its growth and survival. Here we describe the presence of two gene copies, arranged in tandem, that code for the arginine transporter. Both copies show similar Open Reading Frames (ORFs), which are 93% similar to the L. (L.) donovani AAP3 gene, but their 5' and 3' UTR's have distinct regions. According to quantitative...
متن کاملA Leishmania amazonensis ZIP family iron transporter is essential for parasite replication within macrophage phagolysosomes
Infection of mammalian hosts with Leishmania amazonensis depends on the remarkable ability of these parasites to replicate within macrophage phagolysosomes. A critical adaptation for survival in this harsh environment is an efficient mechanism for gaining access to iron. In this study, we identify and characterize LIT1, a novel L. amazonensis membrane protein with extensive similarity to IRT1, ...
متن کاملArginase expression modulates nitric oxide production in Leishmania (Leishmania) amazonensis
BACKGROUND Arginase is an enzyme that converts L-arginine to urea and L-ornithine, an essential substrate for the polyamine pathway supporting Leishmania (Leishmania) amazonensis replication and its survival in the mammalian host. L-arginine is also the substrate of macrophage nitric oxide synthase 2 (NOS2) to produce nitric oxide (NO) that kills the parasite. This competition can define the fa...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Infection and immunity
دوره 75 6 شماره
صفحات -
تاریخ انتشار 2007