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SODB1 is essential for Leishmania major infection of Macrophages and Pathogenesis in Mice.
In: PLoS Neglected Tropical Diseases, Jg. 12 (2018-10-29), Heft 10, S. 1-20
Online
academicJournal
Zugriff:
Leishmania species are sand fly-transmitted protozoan parasites that cause leishmaniasis, neglected tropical diseases that affect millions of people. Leishmania amastigotes must overcome a variety of host defenses, including reactive oxygen species (ROS) produced by the NADPH oxidase. Leishmania species encode three superoxide dismutases (SODs): the mitochondrial SODA and two glycosomal SODs (SODB1 and SODB2). SODs are metalloenzymes that function in antioxidant defense by converting superoxide to oxygen and hydrogen peroxide. Here, we investigated a role for SODB1 in Leishmania infection of macrophages and virulence in mice. We found that a single allele deletion of SODB1 (SODB1/⊗sodb1) had minimal effects on the replication of axenically-grown L. major promastigotes or differentiation to infective metacyclic promastigotes. Disruption of a single SODB1 allele also did not affect L. donovani differentiation to amastigotes induced axenically, or the replication of axenically-grown L. donovani promastigotes and amastigotes. In contrast, the persistence of SODB1/⊗sodb1 L. major in WT macrophages was impaired, and the development of cutaneous lesions in SODB1/⊗sodb1 L. major-infected C57BL/6 and BALB/c mice was strongly reduced. The reduced disease severity in mice was associated with reduced burdens of SODB1/⊗sodb1 L. major parasites in the foot at late, but not early times post-inoculation, as well as an impaired capacity to disseminate from the site of inoculation. Collectively, these data suggest that SODB1 is critical for L. major persistence in macrophages and virulence in mice. [ABSTRACT FROM AUTHOR]
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SODB1 is essential for Leishmania major infection of Macrophages and Pathogenesis in Mice.
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Autor/in / Beteiligte Person: | Davenport, Bennett J. ; Martin, Casey G. ; Beverley, Stephen M. ; Orlicky, David J. ; Vazquez-Torres, Andres ; Morrison, Thomas E. |
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Zeitschrift: | PLoS Neglected Tropical Diseases, Jg. 12 (2018-10-29), Heft 10, S. 1-20 |
Veröffentlichung: | 2018 |
Medientyp: | academicJournal |
ISSN: | 1935-2727 (print) |
DOI: | 10.1371/journal.pntd.0006921 |
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