<scp>l</scp>-Arginine and Cationic Amino Acid Transporter 2B Regulate Growth and Survival of<i>Leishmania amazonensis</i>Amastigotes in Macrophages

Wanasen, Nanchaya; MacLeod, Carol L.; Ellies, Lesley G.; Soong, Lynn

doi:10.1128/iai.00026-07

Cited by 63 publications

(70 citation statements)

References 41 publications

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“…The rust fungus Uromyces fabae induces expression of a general amino acid permease, UtAAT3, in haustoria to acquire amino acids from the leaf apoplast (Struck et al 2004). The expression of the cationic amino acid transporter CAT2B from mouse is upregulated during Leishmania amazonensis infection, thereby providing the arginine necessary for proliferation of the parasite (Wanasen et al 2007). The aromatic and neutral amino acid transporter AtANT1 affects the aphid-Arabidopsis relationship by influencing the ingestion rate of the aphid (Hunt et al 2006).…”

Section: Discussionmentioning

confidence: 99%

The Amino Acid Permeases AAP3 and AAP6 Are Involved in Root-Knot Nematode Parasitism of Arabidopsis

Marella

Nielsen

Schachtman

et al. 2013

MPMI

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The root-knot nematode, Meloidogyne incognita, is an obligate parasite which depends entirely on the host plant for its nutrition. Root-knot nematodes induce the formation of a highly specialized feeding site consisting of several giant cells surrounded by a network of vascular tissues. Nutrients, including amino acids and sugars, are transferred apoplastically from the vascular tissues to the feeding site. Using Arabidopsis thaliana lacking the vascular-expressed amino acid permeases (AAP) AAP3 or AAP6, we demonstrate that disruption of amino acid transport can affect nematode parasitism. Nematode infestation levels are significantly reduced on the aap3 and aap6 mutants. AAP3 and AAP6 act distinctly in the transport of amino acids to the feeding site, as demonstrated by differences in their carrying capacity profiles. Furthermore, analyses of promoter: β-glucuronidase lines show different expression patterns for AAP3 and AAP6 in infected roots. In the aap3-3 mutant, part of the decrease in infestation is connected to a defect in early infection, where juveniles enter but then leave the root. Both aap3-3 and aap6-1 produce fewer females and produce more adult male nematodes. Additionally, detrimental effects are observed in the nematodes harvested from aap3-3 and aap6-1 mutants, including decreased egg hatching and infectivity and lower levels of lipid reserves. The transport of amino acids by AAP3 and AAP6 is important for nematode infection and success of the progeny.

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Section: Discussionmentioning

confidence: 99%

The Amino Acid Permeases AAP3 and AAP6 Are Involved in Root-Knot Nematode Parasitism of Arabidopsis

Marella

Nielsen

Schachtman

et al. 2013

MPMI

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“…The most relevant CAT member involved in MΦ functions is CAT-2, which can be expressed in two splice variants. CAT-2A is constitutively expressed in the liver and muscle cells [27], whereas the expression level CAT-2B is inducible in MΦs and strongly unregulated by IFN-γ, IFN-γ coupling with LPS, IL-4, and GM-CSF [28][29][30]. In the context of Leishmania infection, the expression and function of CAT-2B in MΦs are critical, because CAT-2B-mediated L-arginine transport potentially affects both iNOS and the arginase pathways.…”

Section: L-arginine Metabolism and Transport In Mammalian Cells Espementioning

confidence: 99%

“…Although these studies demonstrated the importance of CAT-2B in MΦ activities, there is limited information on a direct role of CAT-2B in Leishmania infection. Our recent study on L. amazonensis infection has shown that both Th1 (IFN-γ/LPS)-mediated killing and Th2 (IL-4)-mediated growth enhancement of amastigotes were suppressed in peritoneal MΦs derived from CAT-2B knockout mice [28]. Given that IFN-γ alone can enhance the growth of L. amazonensis amastigotes in MΦs [31], it is interesting to find that IFN-γ-mediated growth enhancement was also diminished in CAT-2B-deficient MΦs [28], suggesting that L-arginine transport via CAT-2B can significantly influence the outcome of Leishmania infection (Fig.…”

Section: L-arginine Metabolism and Transport In Mammalian Cells Espementioning

confidence: 99%

L-arginine metabolism and its impact on host immunity against Leishmania infection

2007

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Leishmaniasis is a vector-borne disease found in many countries worldwide. The causative agent of the disease, Leishmania spp., lives as an obligate intracellular parasite within mammalian hosts. Since tissue macrophages are major target cells for parasite replication, the outcome of infection depends largely on the activation status of these cells. L-arginine is a crucial amino acid required for both nitric oxide (NO)-mediated parasite killing and polyamine-mediated parasite replication. This review highlights the significance of L-arginine as a factor determining the outcomes of Leishmania infection in vitro and its influences on host immune responses in vivo. Various therapeutic approaches targeting L-arginine metabolic pathways during infections with Leishmania are also discussed.

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“…On the other hand, CD4 + T cells with characteristics of Th1 cells are thought to be associated with pathogenesis of L. amazonensis infection in C57BL/6 mice [16]. Besides, IFN-γ can promote L. amazonensis replication in macrophages in vitro in certain conditions by induction of the expression of cationic amino acid transporter 2B (CAT2B) that transports L-arginine, which is used directly by the parasite for growth [17]. Therefore, we are now investigating if IL-18 is contributing to susceptibility to L. amazonensis by inducing pathogenic T cell subsets.…”

Section: Discussionmentioning

confidence: 99%

IL-18 contributes to susceptibility to Leishmania amazonensis infection by macrophage-independent mechanisms

et al. 2015

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We evaluated the role of IL-18 during Leishmania amazonensis infection in C57BL/6 mice, using IL-18KO mice. We showed that IL-18 is involved in susceptibility to L. amazonensis, since IL-18KO mice presented reduced lesions and parasite loads. Because macrophages are the host cells of the parasite, we investigated if macrophages were involved in IL-18-mediated susceptibility to L. amazonensis. We showed that macrophages obtained from WT or IL-18KO responded similarly to L. amazonensis infection. Moreover, we showed that C57BL/6 macrophages do not respond to IL-18, since they do not express IL-18R. Therefore, macrophages are not involved in IL-18-mediated susceptibility to L. amazonensis.

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l-Arginine and Cationic Amino Acid Transporter 2B Regulate Growth and Survival ofLeishmania amazonensisAmastigotes in Macrophages

Cited by 63 publications

References 41 publications

The Amino Acid Permeases AAP3 and AAP6 Are Involved in Root-Knot Nematode Parasitism of Arabidopsis

The Amino Acid Permeases AAP3 and AAP6 Are Involved in Root-Knot Nematode Parasitism of Arabidopsis

L-arginine metabolism and its impact on host immunity against Leishmania infection

IL-18 contributes to susceptibility to Leishmania amazonensis infection by macrophage-independent mechanisms

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