Resolution of Cutaneous Leishmaniasis and Persistence of Leishmania major in the Absence of Arginase 1

Beitrag in einer Fachzeitschrift


Details zur Publikation

Autorinnen und Autoren: Paduch K, Debus A, Rai B, Schleicher U, Bogdan C
Zeitschrift: Journal of Immunology
Jahr der Veröffentlichung: 2019
Band: 202
Heftnummer: 5
Seitenbereich: 1453-1464
ISSN: 0022-1767


Abstract

Arginase (Arg) 1 is expressed by hematopoietic (e.g., macrophages) and nonhematopoietic cells (e.g., endothelial cells) and converts L-arginine into ornithine and urea. The enzyme is implicated in tissue repair but also antagonizes the production of NO by type 2 NO synthase in myeloid cells and thereby impedes the control of intracellular parasites such as Leishmania major. In this study, we tested whether Arg1 is required for spontaneous healing of acute cutaneous leishmaniasis in C57BL/6 mice and for lifelong parasite persistence in draining lymph nodes (dLNs) of healed mice. In vitro, bone marrow-derived macrophages and lymphoid endothelial cells readily expressed Arg1 in response to IL-4 and/or IL-13, whereas skin or dLN fibroblasts failed to do so, even during hypoxia. In vivo, Arg1 was found in skin lesions and, to a much lower extent, also in dLNs of acutely infected C57BL/6 mice but became undetectable at both sites after healing. Deletion of Arg1 in hematopoietic and endothelial cells using Tie2Cre(+/-) Arg1(fl/fl) C57BL/6 mice abolished the expression of Arg1 in skin lesions and dLNs but did not affect development and resolution of skin lesions, parasite burden, NO production, or host cell tropism of L. major during the acute or persistent phase of infection. Similar to wild-type controls, parasites persisting in Arg1-deficient mice favored NO synthase 2-negative areas and mainly resided in myeloid cells and fibroblasts. We conclude that Arg1 expression by hematopoietic and endothelial cells is completely dispensable for clinical resolution of cutaneous leishmaniasis and for long-term persistence of L. major.


FAU-Autorinnen und Autoren / FAU-Herausgeberinnen und Herausgeber

Bogdan, Christian Prof. Dr.
Lehrstuhl für Mikrobiologie und Infektionsimmunologie
Paduch, Katrin
Lehrstuhl für Mikrobiologie und Infektionsimmunologie
Rai, Baplu
Mikrobiologisches Institut - Klinische Mikrobiologie, Immunologie und Hygiene
Schleicher, Ulrike PD Dr.
Mikrobiologisches Institut - Klinische Mikrobiologie, Immunologie und Hygiene


Zitierweisen

APA:
Paduch, K., Debus, A., Rai, B., Schleicher, U., & Bogdan, C. (2019). Resolution of Cutaneous Leishmaniasis and Persistence of Leishmania major in the Absence of Arginase 1. Journal of Immunology, 202(5), 1453-1464. https://dx.doi.org/10.4049/jimmunol.1801249

MLA:
Paduch, Katrin, et al. "Resolution of Cutaneous Leishmaniasis and Persistence of Leishmania major in the Absence of Arginase 1." Journal of Immunology 202.5 (2019): 1453-1464.

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Zuletzt aktualisiert 2019-08-03 um 09:08