@article{fdi:010065303,
  title = {{N}rf2-driven {CD}36 and {HO}-1 gene expression in circulating monocytes correlates with favourable clinical outcome in pregnancy-associated malaria},
  author = {{A}ubouy, {A}gn{\`e}s and {O}lagnier, {D}. and {B}ertin, {G}wladys and {E}zinmegnon, {S}. and {M}ajorel, {C}larisse and {M}imar, {S}. and {M}assougbodji, {A}. and {D}eloron, {P}hilippe and {P}ipy, {B}. and {C}oste, {A}.},
  editor = {},
  language = {{ENG}},
  abstract = {{B}ackground: {P}regnancy-associated malaria ({PAM}) constitutes one of the most severe forms of malaria infection leading to fetal growth restriction and high risk of infant death. {T}he 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. {I}mportantly, {CD}36(+) monocytes/macrophages are also thought to participate in the tight control of the pro-and anti-inflammatory responses following {P}lasmodium detection through elimination of apoptotic cells and malaria-infected erythrocytes, internalization and recycling of oxidized forms of low-density lipoprotein and collaboration with {TLR}2 in pro-inflammatory response. {I}nterestingly, previous work demonstrated that {CD}36 expression was upregulated on inflammatory macrophages following stimulation of the {N}rf2 transcription factor, whilst the {PPAR}. pathway was inhibited and non-functional in the same inflammatory conditions. {T}his current study examined the possible role of {N}rf2-driven gene expression, {CD}36 and {H}aem-{O}xygenase-1 ({HO}-1), in {PAM} clinical outcomes. {M}ethods: {C}linical data and biological samples including peripheral blood mononuclear cells were collected from 27 women presenting {PAM}. {P}olychromatic flow cytometry was used to characterize innate immune cell subpopulations and quantify {CD}36 protein expression level on monocytes. m{RNA} levels of {CD}36, {PPAR}., {N}rf2 and {HO}-1 were determined by q{PCR} and related to clinical outcomes. {F}inally, the capacity of monocytes to modulate {CD}36 expression upon rosiglitazone or sulforaphane treatment, two respective {PPAR}. or {N}rf2 activators, was also investigated. {R}esults: {T}he {CD}36 receptor, mostly expressed by {CD}14(+) circulating monocytes, statistically correlated with increased infant birth weights. {I}nterestingly, m{RNA} levels of the transcription factor {N}rf2 and the enzyme {HO}-1 also correlated with lower parasitaemia and increased infant birth weight, while {PPAR}. m{RNA} levels did not. {F}inally, monocytes isolated from low infant birth weight pregnant women were capable of up-regulating {CD}36 via the {N}rf2 pathway ex vivo. {C}onclusions: {A}ltogether these results suggest that {N}rf2-driven {CD}36 and {HO}-1 expression on innate immune cells could contribute to a protective and detoxifying mechanism during {PAM}. {M}ore powered and mechanistical studies are however needed to strengthen the conclusions of this study.},
  keywords = {{P}regnancy-associated malaria ; {C}linical outcomes ; {M}onocytes ; {CD}36 ; {N}rf2 ; {HO}-1 ; {BENIN}},
  booktitle = {},
  journal = {{M}alaria {J}ournal},
  volume = {14},
  numero = {},
  pages = {art. 358 [11 p.]},
  ISSN = {1475-2875},
  year = {2015},
  DOI = {10.1186/s12936-015-0888-8},
  URL = {https://www.documentation.ird.fr/hor/fdi:010065303},
}