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Sci Rep. 2017 Feb 9;7:42243. doi: 10.1038/srep42243.

The antimicrobial molecule trappin-2/elafin has anti-parasitic properties and is protective in vivo in a murine model of cerebral malaria.

Author information

1
Unité de génétique fonctionnelle des maladies infectieuses and CNRS Unité de recherche associée 3012; Paris, 75015, France.
2
Unité de Défense Innée et Inflammation, Institut Pasteur, 25 rue du Dr Roux, Paris, 75015, France.
3
INSERM U874, Institut Pasteur.
4
INSERM U1152, Faculté de Médicine site Bichat, Université Paris Diderot, Université Sorbonne Paris-Cité, 16, rue Henri Huchard, Paris, 75018, France.
5
Institut Pasteur, Unité de Biologie des Interactions Hôte Parasites, CNRS ERL9195 and INSERM U1201, Paris F-75015, France.
6
CNRS ERL9195 and INSERM U1201, Paris F-75015, France.
7
INSERM U1201, Paris F-75015, France.
8
TheVac4all initiative, Institut Cochin, Paris, France.

Abstract

According to the WHO, and despite reduction in mortality rates, there were an estimated 438 000 malaria deaths in 2015. Therefore new antimalarials capable of limiting organ damage are still required. We show that systemic and lung adenovirus (Ad)-mediated over-expression of trappin-2 (T-2) an antibacterial molecule with anti-inflammatory activity, increased mice survival following infection with the cerebral malaria-inducing Plasmodium berghei ANKA (PbANKA) strain. Systemically, T-2 reduced PbANKA sequestration in spleen, lung, liver and brain, associated with a decrease in pro-inflammatory cytokines (eg TNF-α in spleen and lung) and an increase in IL-10 production in the lung. Similarly, local lung instillation of Ad-T-2 resulted in a reduced organ parasite sequestration and a shift towards an anti-inflammatory/repair response, potentially implicating monocytes in the protective phenotype. Relatedly, we demonstrated in vitro that human monocytes incubated with Plasmodium falciparum-infected red blood cells (Pf-iRBCs) and IgGs from hyper-immune African human sera produced T-2 and that the latter colocalized with merozoites and inhibited Pf multiplication. This array of data argues for the first time for the potential therapeutic usefulness of this host defense peptide in human malaria patients, with the aim to limit acute lung injury and respiratory distress syndrom often observed during malaria episodes.

PMID:
28181563
PMCID:
PMC5299836
DOI:
10.1038/srep42243
[Indexed for MEDLINE]
Free PMC Article

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