Exposure to diesel exhaust particle extracts (DEPe) impairs some polarization markers and functions of human macrophages through activation of AhR and Nrf2

PLoS One. 2015 Feb 24;10(2):e0116560. doi: 10.1371/journal.pone.0116560. eCollection 2015.


Macrophages (MΦ), well-known to play an important role in immune response, also respond to environmental toxic chemicals such as diesel exhaust particles (DEP). Potential effects of DEPs towards MΦ polarization, a key hall-mark of MΦ physiology, remain however poorly documented. This study was therefore designed to evaluate the effects of a reference DEP extract (DEPe) on human MΦ polarization. Human blood monocytes-derived MΦ were incubated with IFNγ+LPS or IL-4 to obtain M1 and M2 subtypes, respectively; a 24 h exposure of polarizing MΦ to 10 μg/ml DEPe was found to impair expression of some macrophagic M1 and M2 markers, without however overall inhibition of M1 and M2 polarization processes. Notably, DEPe treatment increased the secretion of the M1 marker IL-8 and the M2 marker IL-10 in both MΦ subtypes, whereas it reduced lipopolysaccharide-induced IL-6 and IL-12p40 secretion in M1 MΦ. In M2 MΦ, DEPe exposure led to a reduction of CD200R expression and of CCL17, CCL18 and CCL22 secretion, associated with a lower chemotaxis of CCR4-positive cells. DEPe activated the Nrf2 and AhR pathways and induced expression of their reference target genes such as Hmox-1 and cytochrome P-4501B1 in M1 and M2 MΦ. Nrf2 or AhR silencing through RNA interference prevented DEPe-related down-regulation of IL-6. AhR silencing also inhibited the down-secretion of IL-12p40 and CCL18 in M1- and M2-DEPe-exposed MΦ, respectively. DEPs are therefore likely to alter expression of some M1 and M2 markers in an AhR- and Nrf2-dependent manner; such regulations may contribute to deleterious immune effects of atmospheric DEP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation / drug effects
  • Chemokines / genetics
  • Chemokines / metabolism*
  • Exocytosis
  • Humans
  • Interleukins / genetics
  • Interleukins / metabolism*
  • Macrophage Activation / drug effects
  • Macrophages / drug effects*
  • Macrophages / metabolism
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism*
  • Particulate Matter / toxicity
  • Receptors, Aryl Hydrocarbon / genetics
  • Receptors, Aryl Hydrocarbon / metabolism*
  • Vehicle Emissions / toxicity*


  • Chemokines
  • Interleukins
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Particulate Matter
  • Receptors, Aryl Hydrocarbon
  • Vehicle Emissions

Grant support

This work was supported by “Fondation Coeur et Artères” (FCA 09T3), Institut National de la Santé et de la Recherche Médicale and the University of Rennes 1. MJ is a recipient of a fellow from the French Ministry of Research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.