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

  • RAJEEV RAI (a1), PAUL DYER (a1), SIMON RICHARDSON (a1), LAURENCE HARBIGE (a1) and GIULIA GETTI (a1)...
Summary
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.

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*Corresponding author: Department of Life and Sport Science, University of Greenwich, Chatham Maritime, Kent, ME4 4TB, UK. E-mail: G.T.M.Getti@greenwich.ac.uk
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N. Aguilo , D. Marinova , C. Martin and J. Pardo (2013). ESX-1 induced apoptosis during mycobacterial infection: to be or not be, that is the question. Frontiers in Cellular and Infection Microbiology 3, 88.

K. Akarid , D. Arnoult , J. Micic-Polianski , J. Sif , J. Estaquier and J. Claude Ameisen (2004). Leishmania major mediated prevention of programmed cell death induction in infected macrophages is associated with the repression of mitochondrial release of cytochrome c. Journal of Leukocyte Biology 76, 95103.

J. Alvar , I. D. Vélez , C. Bern , M. Herrero , P. Desjeux , J. Cano , J. Jannin and M. de Boer (2012). Leishmaniasis worldwide and global estimates of its incidence. PLoS ONE 7, pp: e35671.

H. Ashida , H. Mimuro , M. Ogawa , T. Kobayashi , T. Sanada , M. Kim and C. Sasakawa (2011). Cell death and infection: a double-edged sword for host and pathogen survival. Journal of Cell Biology 195, 931942.

Y. Belkaid , S. Mendez , R. Lira , N. Kadambi , G. Milon and D. Sacks (2000). A natural model of Leishmania major infection reveals a prolonged silent phase of parasite amplification in the skin before the onset of lesion formation and immunity. Journal of Immunology 165, 969977.

E. Bifeld and J. Clos (2015). The genetics of Leishmania virulence . Medical Microbiology and Immunology 204, 619634.

G. I. Byrne and D. M. Ojcius (2004). Chlamydia and apoptosis: life and death decisions of an intracellular pathogen. Nature Reviews Microbiology 2, 802808.

P. Cameron , A. McGachy , M. Anderson , A. Paul , G. H. Coombs , J. C. Mottram , J. Alexander and R. Plevin (2004). Inhibition of Lipopolysaccharide induced macrophage IL-12 production by Leishmania mexicana amastigotes: the role of cysteine peptidases and the NF-kB signaling pathway. Journal of Immunology 173, 32973304.

J. P. DaMata , B. P. Mendes , K. Maciel-Lima , C. A. Menezes , W. O. Dutra , L. P. Sousa and M. F. Horta (2015). Distinct macrophages fates after in vitro infection with different species of Leishmania: induction of apoptosis of Leishmania (Leishmania) amazonensis, but not by Leishmania (Viannia) guyanensis . PLOS ONE 10, pp: e0141196.

M. Dominguez , I. Moreno , C. Aizpurua and A. Torano (2003). Early mechanisms of Leishmania infection in human blood. Microbes and Infection 5, 507513.

M. J. Donovan , B. Z. Maciuba , C. E. Mahan and M. A. McDowell (2009). Leishmania infection inhibits cycloheximide induced macrophage apoptosis in a strain dependent manner. Experimental Parasitology 123, 5864.

N. Friedrich , M. Hagedorn , D. Soldati-Favre and T. Soldati (2012). Prison break: pathogens’ strategies to egress from host cells. Microbiology and Molecular Biology Reviews 76, 707720.

G. Getti , R. A. Cheke and D. P. Humber (2008). Induction of apoptosis in host cells: a survival mechanism for Leishmania parasites? Parasitology 135, 13911399.

D. J. Gregory , M. Godbout , I. Contreras , G. Forget and M. Olivier (2008). A novel form of NF-kB is induced by Leishmania infection: involvement in macrophage gene expression. European Journal of Immunology 38, 10711081.

E. Groppelli , S. Starling and C. Jolly (2015). Contact-induced mitochondrial polarization supports HIV-1 virological synapse formation. Journal of Virology 89, 1424.

M. Hagedorn , K. H. Rohde , D. G. Russell and T. Soldati (2009). Infection by tubercular mycobacteria is spread by nonlytic ejection from their amoeba hosts. Science 323, 17291733.

C. H. C. Hsiao , N. Ueno , J. Q. Shao , K. R. Schroeder , K. C. Moore , J. E. Donelson and M. E. Wilson (2011). The effects of macrophage source on the mechanism of phagocytosis and intracellular survival of Leishmania . Microbes and Infection 13, 10331044.

H. L. Huang , H. W. Hsing , T. C. Lai , Y. W. Chen , T. R. Lee , H. T. Chan , P. C. Lyu , C. L. Wu , Y. C. Lu , S. T. Lin , C. W. Lin , C. H. Lai , H. T. Chang , H. C. Chou and H. L. Chan (2010). Trypsin induced proteome alteration during cell subculture in mammalian cells. Journal of Biomedical Science 17, pp 36.

L. Kedzierski (2010). Leishmaniasis Vaccine: where are we today? Journal of Global Infectious Diseases 2, 177185.

N. Kimblin , N. Peters , A. Debrabant , N. Secundino , J. Egen , P. Lawyer , P. Fay , S. Kamhawi and D. Sacks (2008). Quantification of the infectious dose of Leishmania major transmitted to the skin by single sand flies. PNAS 105, 1012510130.

S. Lisi , M. Sisto , A. Acquafredda , R. Spinelli , M. A. Schiavone , V. Mitolo , O. Brandonisio and M. A. Panaro (2005). Infection with Leishmania infantum inhibits actinomycin D induced apoptosis of human monocytic cell line U-937. Journal of Eukaryotic Microbiology 52, 211217.

R. Lodge and A. Descoteaux (2005). Modulation of phagolysosome biogenesis by the lipophosphoglycan of Leishmania . Clinical Immunology 114, 174181.

J. Mi , Z. Li , S. Ni , D. Steinwaerder and A. Liber (2001). Induced apoptosis supports spread of adenovirus vectors in tumours. Human Gene Therapy 12, 13431352.

A. Mißlitz , J. C. Mottram , P. Overath and T. Aebischer (2000). Targeted integration into a rRNA locus results in uniform and high level expression of transgenes in Leishmania amastigotes . Molecular and Biochemical Parasitology 107, 251261.

B. W. Ogunkolade , I. Colomb-Valet , L. Monjour , A. Rhodes-Feuillette , J. P. Abita and D. Froomel (1990). Interactions between the human monocytic leukaemia THP-1 cell line and ld and New World species of Leishmania . Acta Tropica 47, 171176.

A. P. Patel , A. Deacon and G. Getti (2014). Development and validation of four Leishmania species constitutively expressing GFP protein. A model for drug discovery and disease pathogenesis studies. Parasitology 141, 501510.

F. Real , P. T. V. Florentina , L. C. Reis , E. M. Ramos-Sanchez , P. S. T. Veras , H. Goto and R. A. Mortara (2014). Cell-to-cell transfer of Leishmania amazonensis amastigotes is mediated by immunomodulatory LAMP-rich parasitophorous extrusions. Cellular Microbiology 16, 15491564.

S. C. Richardson , K. L. Wallom , E. L. Ferguson , S. P. Deacon , M. W. Davies , A. J. Powell , R. C. Piper and R. Duncan (2008). The use of fluorescence microscopy to define polymer localisation to the late endocytic compartments in cells that are targets for drug delivery. Journal of Controlled Release 127, 111.

M. E. Rogers , T. IIg , A. V. Nikolaev , M. A. Ferguson and P. A. Bates (2004). Transmission of cutaneous leishmaniasis by sand flies is enhanced by regurgitation of fPPG. Nature 430, 463467.

A. Ruhland , N. Leal and P. E. Kima (2007). Leishmania promastigotes activate PI3K/AKT signaling to confer host cell resistance to apoptosis. Cellular Microbiology 9, 8496.

K. Seifert , P. Escobar and S. L. Croft (2010). In vitro activity of anti-leishmanial drugs against Leishmania donovani is host cell dependent. Journal of Antimicrobial Chemotherapy 65, 508511.

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Parasitology
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