The human heart contains distinct macrophage subsets with divergent origins and functions

Geetika Bajpai1, Caralin Schneider1, Nicole Wong1

  • 1Center for Cardiovascular Research, Division of Cardiology, Department of Medicine, Washington University School of Medicine, Saint Louis, MO, USA.

Nature Medicine
|June 13, 2018
PubMed

Insights

Human heart macrophages show distinct types, CCR2- and CCR2+, with different origins and functions. This macrophage heterogeneity is crucial for immune responses and impacts heart failure patients.

Area of Science:

  • Immunology
  • Cardiology
  • Cell Biology

Background:

  • Tissue macrophage heterogeneity is key in mouse immunity, but poorly understood in humans.
  • Mouse heart macrophages exist as CCR2- (reparative) and CCR2+ (inflammatory) subsets with distinct origins and functions.

Purpose of the Study:

  • To investigate macrophage heterogeneity in the human myocardium.
  • To determine the origins, repopulation, and functional properties of human heart macrophage subsets.

Main Methods:

  • Analysis of sex-mismatched heart transplant recipients.
  • Flow cytometry and single-cell RNA sequencing (implied).

Main Results:

  • Human myocardium contains distinct CCR2- and CCR2+ macrophage subsets.
  • CCR2- macrophages are tissue-resident and proliferate locally.
  • CCR2+ macrophages are derived from monocyte recruitment and proliferation.
  • CCR2- and CCR2+ macrophages exhibit analogous functions to mouse reparative and inflammatory subsets, respectively.
  • CCR2+ macrophage abundance correlates with left ventricular remodeling and systolic function in heart failure.

Conclusions:

  • Human heart macrophage populations exhibit functional heterogeneity.
  • Macrophage heterogeneity plays a significant role in human cardiac immune responses and disease states like heart failure.

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