Comparative study of the ability of Leishmania mexicana promastigotes and amastigotes to alter macrophage signalling and functions

Abu-Dayyeh, I., Hassani, K., Westra, E.R., Mottram, J.C. and Olivier, M. (2010) Comparative study of the ability of Leishmania mexicana promastigotes and amastigotes to alter macrophage signalling and functions. Infection and Immunity, 78(6), pp. 2438-2445. (doi:10.1128/IAI.00812-09)

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Publisher's URL: http://dx.doi.org/10.1128/IAI.00812-09

Abstract

Leishmania alternates between two morphologically different stages: promastigotes and amastigotes. While the majority of reports focused on how the promastigote form can alter macrophage signalling and function, fewer reports investigated signalling alterations mediated by amastigotes, and comparative studies are lacking. In this study, we performed a comparison between the ability of both forms of the parasite to alter macrophage signalling and functions. Here, we show that promastigotes and amastigotes were both able to rapidly activate host protein tyrosine phosphatases (PTPs), importantly the Src-homology 2 domain-containing PTP (SHP-1). However, we found that PTP-1B is specifically activated by promastigote but not amastigote infection and that lmcpb-/- promastigotes were no longer able to activate PTP-1B. We also show a similarity in the way promastigotes and amastigotes inactivate the transcription factors (TFs) STAT-1{alpha} and AP-1, but differences in the modulation of NF-{kappa}B with promastigotes cleaving the p65 subunit generating a smaller p35 subunit while amastigotes fully degrading the p65 subunit with no p35 production. Importantly, we show that the cysteine proteinase LmCPb plays a key role in the alteration of NF-{kappa}B, STAT-1{alpha}, and AP-1 by promastigote and amastigote infections, ultimately leading to the inability of these TFs to translocate to the nucleus in response to IFN-{gamma} stimulation and thus contributing to the ability of both parasite forms to effectively block IFN-{gamma}-mediated NO production in macrophages.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Mottram, Professor Jeremy
Authors: Abu-Dayyeh, I., Hassani, K., Westra, E.R., Mottram, J.C., and Olivier, M.
Subjects:Q Science > QR Microbiology > QR180 Immunology
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Infection and Immunity
ISSN:0019-9567
ISSN (Online):1098-5522
Published Online:05 April 2010

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
417381The immunobiological activity of the Leishmania cysteine peptidases and their natural inhibitorsJeremy MottramWellcome Trust (WELLCOME)079356/CB/06/ZInfection Immunity and Inflammation Life Sciences