Hypoxia in Leishmania major skin lesions impairs the NO-dependent leishmanicidal activity of macrophages

Mahnke A, Meier RJ, Schatz V, Hofmann J, Castiglione K, Schleicher U, Wolfbeis OS, Bogdan C, Jantsch J (2014)

Publication Type: Journal article

Publication year: 2014

Journal

Journal of Investigative Dermatology Nature Publishing Group: Open Access Hybrid Model Option A

Publisher: Nature Publishing Group: Open Access Hybrid Model Option A

Book Volume: 134

Pages Range: 2339-46

Journal Issue: 9

DOI: 10.1038/jid.2014.121

Abstract

Cure of infections with Leishmania major is critically dependent on the ability of macrophages to induce the type 2 nitic oxide (NO) synthase (NOS2) that produces high levels of NO in the presence of ample oxygen. Therefore, we analyzed the oxygen levels found in leishmanial skin lesions and their effect on the NOS2-dependent leishmanicidal activity of macrophages (M?). When L. major skin lesions of self-healing C57BL/6 mice reached their maximum size, the infected tissue displayed low oxygen levels (pO2~21 Torr). M? activated under these oxygen tensions failed to produce sufficient amounts of NO to clear L. major. Nos2-deficient and hypoxic wild-type macrophages displayed a similar phenotype. Killing was restored when M? were reoxygenated or exposed to a NO donor. The resolution of the lesion in C57BL/6 mice was paralleled by an increase of lesional pO2. When mice were kept under normobaric hypoxia, this caused a persistent suppression of the lesional pO2 and a concurrent increase of the parasite load. In Nos2-deficient mice, there was no effect of atmospheric hypoxia. Low oxygen levels found at leishmanial skin lesions impaired the NOS2-dependent leishmanicidal activity of M?. Hence, tissue oxygenation represents an underestimated local milieu factor that participates in the persistence of Leishmania.

Authors with CRIS profile

Alexander Mahnke Lehrstuhl für Mikrobiologie und Infektionsimmunologie Valentin Schatz Lehrstuhl für Genetik Ulrike Schleicher Institute of Microbiology – Clinical Microbiology, Immunology and Hygiene Christian Bogdan Lehrstuhl für Mikrobiologie und Infektionsimmunologie

Involved external institutions

Universität Regensburg DE Germany (DE)

How to cite

APA:

Mahnke, A., Meier, R.J., Schatz, V., Hofmann, J., Castiglione, K., Schleicher, U.,... Jantsch, J. (2014). Hypoxia in Leishmania major skin lesions impairs the NO-dependent leishmanicidal activity of macrophages. Journal of Investigative Dermatology, 134(9), 2339-46. https://doi.org/10.1038/jid.2014.121

MLA:

Mahnke, Alexander, et al. "Hypoxia in Leishmania major skin lesions impairs the NO-dependent leishmanicidal activity of macrophages." Journal of Investigative Dermatology 134.9 (2014): 2339-46.

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