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Apoptotic induction induces Leishmania aethiopica and L. mexicana spreading in terminally differentiated THP-1 cells

Published online by Cambridge University Press:  24 July 2017

RAJEEV RAI ,
PAUL DYER ,
SIMON RICHARDSON ,
LAURENCE HARBIGE  and
GIULIA GETTI Open the ORCID record for GIULIA GETTI [Opens in a new window]
RAJEEV RAI
Affiliation:
Department of Life and Sport Science, University of Greenwich, Chatham Maritime, Kent, ME4 4TB, UK
PAUL DYER
Affiliation:
Department of Life and Sport Science, University of Greenwich, Chatham Maritime, Kent, ME4 4TB, UK
SIMON RICHARDSON
Affiliation:
Department of Life and Sport Science, University of Greenwich, Chatham Maritime, Kent, ME4 4TB, UK
LAURENCE HARBIGE
Affiliation:
Department of Life and Sport Science, University of Greenwich, Chatham Maritime, Kent, ME4 4TB, UK
GIULIA GETTI*
Affiliation:
Department of Life and Sport Science, University of Greenwich, Chatham Maritime, Kent, ME4 4TB, UK
*
*Corresponding author: Department of Life and Sport Science, University of Greenwich, Chatham Maritime, Kent, ME4 4TB, UK. E-mail: [email protected]
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Summary

Leishmaniasis develops after parasites establish themselves as amastigotes inside mammalian cells and start replicating. As relatively few parasites survive the innate immune defence, intracellular amastigotes spreading towards uninfected cells is instrumental to disease progression. Nevertheless the mechanism of Leishmania dissemination remains unclear, mostly due to the lack of a reliable model of infection spreading. Here, an in vitro model representing the dissemination of Leishmania amastigotes between human macrophages has been developed. Differentiated THP-1 macrophages were infected with GFP expressing Leishmania aethiopica and Leishmania mexicana. The percentage of infected cells was enriched via camptothecin treatment to achieve 64·1 ± 3% (L. aethiopica) and 92 ± 1·2% (L. mexicana) at 72 h, compared to 35 ± 4·2% (L. aethiopica) and 36·2 ± 2·4% (L. mexicana) in untreated population. Infected cells were co-cultured with a newly differentiated population of THP-1 macrophages. Spreading was detected after 12 h of co-culture. Live cell imaging showed inter-cellular extrusion of L. aethiopica and L. mexicana to recipient cells took place independently of host cell lysis. Establishment of secondary infection from Leishmania infected cells provided an insight into the cellular phenomena of parasite movement between human macrophages. Moreover, it supports further investigation into the molecular mechanisms of parasites spreading, which forms the basis of disease development.

Keywords

In vitro modelspreadingLeishmania aethiopicaLeishmania mexicanahuman monocytesinfectionTHP-1Retinoic acid
Type
Research Article
Information
Parasitology , Volume 144 , Issue 14 , December 2017 , pp. 1912 - 1921
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Copyright
Copyright © Cambridge University Press 2017 

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