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

Rai, R; Dyer, P; Richardson, S; Harbige, L; Getti, G; (2017) Apoptotic induction induces Leishmania aethiopica and L. mexicana spreading in terminally differentiated THP-1 cells. Parasitology , 144 (14) pp. 1912-1921. 10.1017/S0031182017001366. Green open access

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Abstract

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.

Type: Article
Title: Apoptotic induction induces Leishmania aethiopica and L. mexicana spreading in terminally differentiated THP-1 cells
Open access status: An open access version is available from UCL Discovery
DOI: 10.1017/S0031182017001366
Publisher version: http://doi.org/10.1017/S0031182017001366
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: In vitro model, spreading, Leishmania aethiopica, Leishmania mexicana, human monocytes, infection, THP-1, Retinoic acid
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/1566825
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