2024-03-29T08:02:42Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/68382022-10-05T13:33:00Zcom_20.500.12105_2060com_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_2061
Repisalud
author
Moreno-Iruela, Inmaculada
author
Dominguez-Rodriguez, Mercedes
author
Cabañes, Dario
author
Aizpurua, Carmen
author
Toraño, Alfredo
funder
Ministerio de Educación y Ciencia (España)
funder
Instituto de Salud Carlos III
funder
Comunidad de Madrid (España)
2018-12-13T10:50:28Z
2018-12-13T10:50:28Z
2010-07-13
PLoS Negl Trop Dis. 2010 Jul;4(7):e743
http://hdl.handle.net/20.500.12105/6838
20644618
10.1371/journal.pntd.0000743
1935-2735
PLoS neglected tropical diseases
The leishmanioses, vector-borne diseases caused by the trypanosomatid protozoan Leishmania, are transmitted to susceptible mammals by infected phlebotomine sand flies that inoculate promastigotes into hemorrhagic pools created in host skin. We assumed that promastigotes are delivered to a blood pool, and analyzed early promastigote interactions (0-5 min) with host components, which lead to parasite endocytosis by blood leukocytes, and to host infection. Promastigotes were incubated with NHS or with heparinized blood in near-physiological conditions, and we used cell radioimmunoassay and flow cytometry to measure the on-rate constants (k(+1)) of promastigote interactions with natural opsonins and erythrocytes. We obtained quantitative data for parasitized cells to determine the time-course of promastigote binding and internalization by blood leukocytes. In these reactions, promastigotes bind natural opsonins, immune adhere to erythrocytes and activate complement cytolysis, which kills approximately 95% of promastigotes by 2 min post-infection. C3-promastigote binding is a key step in opsonization; nascent C3-promastigotes are the substrate for two simultaneous reactions, C3-promastigote immune adherence (IA) to erythrocytes and complement-mediated promastigote killing. The k(+1) for IA was 75-fold greater than that for promastigote killing, showing that IA facilitates promastigote endocytosis and circumvents lysis. At 5 min post-infection, when reaction velocity is still linear and promastigote concentration is not limiting, 17.4% of granulocytes and 10.7% of monocytes had bound promastigotes, of which approximately 50% and approximately 25%, respectively, carried surface-bound (live) or internalized (live and dead) leishmanias. Of other leukocyte types, 8.5% of B cells bound but did not internalize promastigotes, and T cells, NK cells and CD209(+) dendritic cells did not bind parasites. These data show that, once in contact with blood, promastigote invasion of human leukocytes is an extremely rapid and efficient reaction, and suggest that the IA reaction constitutes a central strategy for this parasite in subverting host innate immune defenses.
eng
Kinetic analysis of ex vivo human blood infection by Leishmania
journal article
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URL
https://repisalud.isciii.es/bitstream/20.500.12105/6838/1/KineticAnalysisOfEx_2010.pdf
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KineticAnalysisOfEx_2010.pdf
URL
https://repisalud.isciii.es/bitstream/20.500.12105/6838/3/KineticAnalysisOfEx_2010.pdf.txt
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KineticAnalysisOfEx_2010.pdf.txt