Leishmania major parasite stage-dependent host cell invasion and immune evasion.
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Leishmania major parasite stage-dependent host cell invasion and immune evasion. / Wenzel, Ulrich; Bank, Elena; Florian, Christian; Förster, Sabine; Zimara, Nicole; Steinacker, Jochen; Klinger, Matthias; Reiling, Norbert; Ritter, Uwe; van Zandbergen, Ger.
In: FASEB J, Vol. 26, No. 1, 1, 2012, p. 29-39.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Leishmania major parasite stage-dependent host cell invasion and immune evasion.
AU - Wenzel, Ulrich
AU - Bank, Elena
AU - Florian, Christian
AU - Förster, Sabine
AU - Zimara, Nicole
AU - Steinacker, Jochen
AU - Klinger, Matthias
AU - Reiling, Norbert
AU - Ritter, Uwe
AU - van Zandbergen, Ger
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
KW - Animals
KW - Humans
KW - Female
KW - Mice
KW - Mice, Inbred BALB C
KW - Mice, Inbred C57BL
KW - Microscopy, Electron, Scanning
KW - Axenic Culture/methods
KW - Endocytosis/immunology
KW - Gene Expression/physiology
KW - Host-Parasite Interactions/immunology
KW - Leishmania major/genetics/growth & development/immunology
KW - Leishmaniasis, Cutaneous/immunology/parasitology
KW - Macrophages/immunology/parasitology/ultrastructure
KW - Neutrophils/immunology/parasitology/ultrastructure
KW - Phagocytosis/immunology
KW - Animals
KW - Humans
KW - Female
KW - Mice
KW - Mice, Inbred BALB C
KW - Mice, Inbred C57BL
KW - Microscopy, Electron, Scanning
KW - Axenic Culture/methods
KW - Endocytosis/immunology
KW - Gene Expression/physiology
KW - Host-Parasite Interactions/immunology
KW - Leishmania major/genetics/growth & development/immunology
KW - Leishmaniasis, Cutaneous/immunology/parasitology
KW - Macrophages/immunology/parasitology/ultrastructure
KW - Neutrophils/immunology/parasitology/ultrastructure
KW - Phagocytosis/immunology
M3 - SCORING: Journal article
VL - 26
SP - 29
EP - 39
JO - FASEB J
JF - FASEB J
SN - 0892-6638
IS - 1
M1 - 1
ER -
