Leishmania major parasite stage-dependent host cell invasion and immune evasion

Ulf Alexander Wenzel, Elena Bank, Christian Florian, Sabine Förster, Nicole Zimara, Jochen Steinacker, Matthias Klinger, Norbert Reiling, Uwe Ritter, Ger Van Zandbergen*

*Korrespondierende/r Autor/-in für diese Arbeit
34 Zitate (Scopus)

Abstract

Leishmania pathogenesis is primarily studied using the disease-inducing promastigote stage of Leishmania major. Despite many efforts, all attempts so far have failed to culture the disease-relevant multiplying amastigote stage of L. major. Here, we established a stably growing axenic L. major amastigote culture system that was characterized genetically, morphologically, and by stage-specific DsRed protein expression. We found parasite stage-specific disease development in resistant C57BL/6 mice. Human neutrophils, as first host cells for promastigotes, do not take up amastigotes. In human macrophages, we observed an amastigote-specific complement receptor 3-mediated, endocytotic entry mechanism, whereas promastigotes are taken up by complement receptor 1-mediated phagocytosis. Promastigote infection of macrophages induced the inflammatory mediators TNF, CCL3, and CCL4, whereas amastigote infection was silent and resulted in significantly increased parasite numbers: from 7.1 ± 1.4 (after 3 h) to 20.1 ± 7.9 parasites/cell (after 96 h). Our study identifies Leishmania stage-specific disease development, host cell preference, entry mechanism, and immune evasion. Since the amastigote stage is the disease-propagating form found in the infected mammalian host, the newly developed L. major axenic cultures will serve as an important tool in better understanding the amastigote-driven immune response in leishmaniasis.

OriginalspracheEnglisch
ZeitschriftFASEB Journal
Jahrgang26
Ausgabenummer1
Seiten (von - bis)29-39
Seitenumfang11
ISSN0892-6638
DOIs
PublikationsstatusVeröffentlicht - 01.2012

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