Monocyte responses in the context of Q fever: from a static polarized model to a kinetic model of activation

J Infect Dis. 2013 Sep;208(6):942-51. doi: 10.1093/infdis/jit266. Epub 2013 Jun 24.

Abstract

Background: Q fever is caused by Coxiella burnetii, a bacterium that persists in M2-polarized macrophages. We wondered whether the concept of M1/M2 polarization is applicable to Q fever patients.

Methods: Monocytes from healthy controls were cultured with IFN-γ and IL-4, agonists of M1 and M2 macrophages, respectively, and their gene expression was assessed using whole-genome microarrays. Selected biomarkers were assessed in blood from Q fever patients by real-time reverse transcription polymerase chain reaction (RT-PCR).

Results: Monocytes exhibited early (6-hour) patterns of activation specific to IFN-γ or IL-4 and a late (18-hour) pattern of common activation. Because these responses were not reducible to M1/M2 polarization, we selected biomarkers and tested their relevance in Q fever patients. The early genes NLRC5, RTP4, and RHOH, which were modulated in response to IFN-γ, were up-regulated in patients with acute Q fever, and the expression levels of the late genes ALOX15, CLECSF1, CCL13, and CCL23 were specifically increased in patients with Q fever endocarditis. The RHOH and ALOX15 genes were associated with the activity of acute Q fever and Q fever endocarditis, respectively.

Conclusions: Our results show that the kinetic model of monocyte activation enables a dynamic approach for the evaluation of Q fever patients.

Keywords: Q fever; macrophage; microarray; monocyte; polarization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Aged
  • Biomarkers / blood
  • Case-Control Studies
  • Coxiella burnetii
  • Endocarditis, Bacterial / immunology
  • Gene Expression Regulation
  • Humans
  • Interferon-gamma / immunology
  • Interleukin-4 / immunology
  • Macrophage Activation*
  • Macrophages / immunology
  • Microarray Analysis
  • Middle Aged
  • Monocytes / immunology*
  • Q Fever / immunology*
  • Transcription, Genetic
  • Up-Regulation

Substances

  • Biomarkers
  • Interleukin-4
  • Interferon-gamma