Publications des scientifiques de l'IRD

Aubouy Agnès, Olagnier D., Bertin Gwladys, Ezinmegnon S., Majorel Clarisse, Mimar S., Massougbodji A., Deloron Philippe, Pipy B., Coste A. (2015). Nrf2-driven CD36 and HO-1 gene expression in circulating monocytes correlates with favourable clinical outcome in pregnancy-associated malaria. Malaria Journal, 14, p. art. 358 [11 p.]. ISSN 1475-2875.

Titre du document
Nrf2-driven CD36 and HO-1 gene expression in circulating monocytes correlates with favourable clinical outcome in pregnancy-associated malaria
Année de publication
2015
Type de document
Article référencé dans le Web of Science WOS:000361359300002
Auteurs
Aubouy Agnès, Olagnier D., Bertin Gwladys, Ezinmegnon S., Majorel Clarisse, Mimar S., Massougbodji A., Deloron Philippe, Pipy B., Coste A.
Source
Malaria Journal, 2015, 14, p. art. 358 [11 p.] ISSN 1475-2875
Background: Pregnancy-associated malaria (PAM) constitutes one of the most severe forms of malaria infection leading to fetal growth restriction and high risk of infant death. The severity of the pathology is largely attributed to the recruitment of monocytes and macrophages in the placenta which is evidenced by dysregulated inflammation found in placental blood. Importantly, CD36(+) monocytes/macrophages are also thought to participate in the tight control of the pro-and anti-inflammatory responses following Plasmodium detection through elimination of apoptotic cells and malaria-infected erythrocytes, internalization and recycling of oxidized forms of low-density lipoprotein and collaboration with TLR2 in pro-inflammatory response. Interestingly, previous work demonstrated that CD36 expression was upregulated on inflammatory macrophages following stimulation of the Nrf2 transcription factor, whilst the PPAR. pathway was inhibited and non-functional in the same inflammatory conditions. This current study examined the possible role of Nrf2-driven gene expression, CD36 and Haem-Oxygenase-1 (HO-1), in PAM clinical outcomes. Methods: Clinical data and biological samples including peripheral blood mononuclear cells were collected from 27 women presenting PAM. Polychromatic flow cytometry was used to characterize innate immune cell subpopulations and quantify CD36 protein expression level on monocytes. mRNA levels of CD36, PPAR., Nrf2 and HO-1 were determined by qPCR and related to clinical outcomes. Finally, the capacity of monocytes to modulate CD36 expression upon rosiglitazone or sulforaphane treatment, two respective PPAR. or Nrf2 activators, was also investigated. Results: The CD36 receptor, mostly expressed by CD14(+) circulating monocytes, statistically correlated with increased infant birth weights. Interestingly, mRNA levels of the transcription factor Nrf2 and the enzyme HO-1 also correlated with lower parasitaemia and increased infant birth weight, while PPAR. mRNA levels did not. Finally, monocytes isolated from low infant birth weight pregnant women were capable of up-regulating CD36 via the Nrf2 pathway ex vivo. Conclusions: Altogether these results suggest that Nrf2-driven CD36 and HO-1 expression on innate immune cells could contribute to a protective and detoxifying mechanism during PAM. More powered and mechanistical studies are however needed to strengthen the conclusions of this study.
Plan de classement
Santé : généralités [050] ; Entomologie médicale / Parasitologie / Virologie [052]
Description Géographique
BENIN
Localisation
Fonds IRD [F B010065303]
Identifiant IRD
fdi:010065303
Contact