Review Article | Published:

Cardioimmunology: the immune system in cardiac homeostasis and disease

Abstract

The past few decades have generated growing recognition that the immune system makes an important contribution to cardiac development, composition and function. Immune cells infiltrate the heart at gestation and remain in the myocardium, where they participate in essential housekeeping functions throughout life. After myocardial infarction or in response to infection, large numbers of immune cells are recruited to the heart to remove dying tissue, scavenge pathogens and promote healing. Under some circumstances, immune cells can cause irreversible damage, contributing to heart failure. This Review focuses on the role of the immune system in the heart under both homeostatic and perturbed conditions.

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Acknowledgements

The authors acknowledge K. Joyes for editing the manuscript. This work was funded in part by federal funds from the US National Heart, Lung, and Blood Institute (NHLBI) (HL135752 and HL139598) and the Massachusetts General Hospital Research Scholar Program.

Reviewer information

Nature Reviews Immunology thanks D. Ciháková, S. Epelman and J.-S. Silvestre for their contribution to the peer review of this work.

Author information

Both authors researched data for the article, discussed its content and wrote, reviewed and edited the article.

Competing interests

The authors declare no competing interests.

Correspondence to Filip K. Swirski or Matthias Nahrendorf.

Glossary

Cardiomyocytes

Large muscle cells specific to the heart.

Definitive haematopoiesis

The production of mature blood cells from haematopoietic progenitor cells in the bone marrow that occurs throughout life.

Atrioventricular node

The node that controls the ventricular heart rate and is a major relay station for electrical conduction from atria to ventricles in the heart.

Pericardium

The membrane layer enclosing the heart.

Serosal fluid

Fluid in body cavities such as the pericardium.

Primitive coronary plexus

A developmental stage of the coronary vasculature.

Gap junctions

Intercellular connections formed by connexin proteins that directly connect the cytoplasm of two cells and enable exchange of ions, which electrically couples cardiomyocytes to each other and to macrophages.

Source–sink relationship

An interaction that involves the exchange of charges between excitable cardiomyocytes and passively depolarized macrophages.

Optical tissue clearance

A method by which biological specimens are treated to enable whole organ microscopy.

Sinus node

The pacemaker of the heart, consisting of a cluster of spontaneously depolarizing cells in which electrical impulses are generated.

CD11b DTR mice

Transgenic mice expressing the diphtheria toxin receptor under control of the Cd11b (also known as Itgam) gene promoter, which enables macrophage depletion after injection of non-toxic doses of diphtheria toxin.

Granulation tissue

Newly forming tissue during wound healing that contains leukocytes, stromal cells, extracellular matrix and blood vessels.

Non-reperfused myocardial infarction

An event that occurs when a coronary artery is closed off and not re-opened for blood flow, leading to the ischaemic death of a large number of cardiac cells.

Remote myocardium

The part of the heart that is not directly affected by ischaemia during myocardial infarction.

Ejection fraction

The volume of blood ejected with each heartbeat, which is normalized to the size of the left ventricular cavity.

Sympathetic tone

Innervation by a branch of the autonomous nervous system that increases the output of the heart but also has many other functions, including in the haematopoietic and immune systems.

Dilated cardiomyopathy

Enlargement of the left ventricle leading to heart failure.

Re-entry arrhythmias

Conduction disorders in which the depolarizing wave front circles, often leading to rapid and uncoordinated cardiomyocyte contractions.

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Further reading

Fig. 1: Cardiac anatomy with respect to immune cells.
Fig. 2: Participation of macrophages in normal electrical conduction.
Fig. 3: Immune cells in coronary heart disease.
Fig. 4: Potential immune mechanisms in viral myocarditis.