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Review
. 2008;41(1):15-25.
doi: 10.1007/s12026-007-8012-y.

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

Affiliations
Review

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

Nanchaya Wanasen et al. Immunol Res. 2008.

Abstract

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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Figures

Fig. 1
Fig. 1
L-arginine metabolic pathways and their influence on Leishmania infection. Classical activation of MΦs via stimulation of Th1 cytokines (IFN-γ plus LPS or IFN-γ plus TNF-α) results in an enhanced expression of CAT-2B, increased L-arginine availability and iNOS activity, ultimately leading to parasite killing. Conversely, Th2-mediated activation of MΦs (via IL-4, IL-13, and TGF-β) enhances CAT-2B expression and arginase activity, resulting in parasite growth. In suboptimally activated MΦs (primed by low concentrations of IFN-γ), CAT-2B is moderately induced, but iNOS and arginase remain relatively inactivated, allowing Leishmania amastigotes (Am) to take up and use available L-arginine for their proliferation. While it is unclear which molecules are responsible for the transport of L-arginine across the parasitophorous (PV) membrane, at least one permease, LdAAP3, has been identified as a transporter of L-arginine across the membrane of L. donovani promastigotes. Once inside the amastigotes, L-arginine can be utilized by parasite-derived NOS or arginase. While Leishmania-derived arginase is involved in polyamine synthesis necessary for the parasite growth, the exact role of Leishmania-derived NOS during infection is unclear

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