The antimicrobial molecule trappin-2/elafin has anti-parasitic properties and is protective in vivo in a murine model of cerebral malaria
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 antib...
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Published in | Scientific reports Vol. 7; no. 1; p. 42243 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
09.02.2017
Nature Publishing Group |
Subjects | |
Online Access | Get full text |
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Summary: | 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 (
Pb
ANKA) strain. Systemically, T-2 reduced
Pb
ANKA 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. |
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ISSN: | 2045-2322 2045-2322 |
DOI: | 10.1038/srep42243 |