When Protection Becomes Harm: The Double-Edged Role of Immune Cells in Heart Health

Welcome to the Immune system & Heart Health Series

This is the first in a series of articles where I will explain why the immune system is highly relevant to heart health. With each blog, I will introduce some of the most important scientific literature showing how the immune system regulates both heart function and disease progression. Stay tuned for future posts to continue learning about this fascinating connection!

Introduction

Did you know that your heart harbours immune cells that have been there since birth?

Yes
No, why would we have immune cells in the heart??

We often think of immune cells as warriors that fight infections and clear inflammation in the body. But if that’s their primary role, what are they doing in the heart? Do they serve as protectors, or can they also become harmful?

To answer this question, let’s first break down the different types of immune cells and their functions.

The Immune Subsets in the Heart

The immune system consists of two major arms:

Myeloid cells (Innate immune response)
Lymphoid cells (Adaptive immune response)

Both populations arise from hematopoietic stem cells in the bone marrow.

Myeloid Cells (Innate Immunity)

Myeloid cells are the body’s first responders, crucial in detecting and eliminating threats before they spread.

Neutrophils – The most abundant white blood cells and the body's frontline soldiers. They rapidly migrate to infection sites, engulf bacteria, and release enzymes to destroy them. However, excessive neutrophil activity can cause tissue damage.
Monocytes – Circulate in the bloodstream and respond to infection or injury by migrating into tissues, where they transform into macrophages or dendritic cells.
Macrophages – Found in nearly all tissues, they act as scavengers that engulf and digest pathogens, dead cells, and debris. In the heart, macrophages not only aid in cleanup but also support electrical conduction and tissue repair.
Dendritic Cells – Messengers of the immune system. They capture pathogens and present them to T cells, initiating an adaptive immune response.
Eosinophils & Basophils – Involved in allergic reactions and defense against parasites. They release inflammatory substances like histamine, which help the body respond to external threats.

Lymphoid Cells (Adaptive Immunity)

Lymphoid cells are responsible for long-term immunity and precise immune responses. Unlike myeloid cells, which act immediately, lymphoid cells are more specialized and adaptive.

T Cells (T Lymphocytes) – The commanders of the adaptive immune system. They mature in the thymus and differentiate into specialized subtypes:

CD4+ Helper T Cells – Direct and coordinate immune responses by activating other immune cells.
CD8+ Cytotoxic T Cells – Destroy infected or damaged cells to prevent the spread of disease.
Regulatory T Cells (Tregs) – Help prevent excessive immune reactions that could lead to autoimmunity.

B Cells (B Lymphocytes) – The antibody producers of the immune system. They mature in the bone marrow and, upon activation, differentiate into plasma cells, which produce antibodies that neutralize pathogens.

Natural Killer (NK) Cells – A hybrid between innate and adaptive immunity, NK cells target and destroy infected or abnormal cells, such as cancerous or virus-infected cells, without prior sensitization.

The Journey from Bone Marrow to Their Posts

Immune cells originate from hematopoietic stem cells in the bone marrow. Once formed, they follow specific pathways:

Myeloid cells (neutrophils, monocytes, macrophages, dendritic cells) circulate in the bloodstream and migrate into tissues, including the heart, where they reside and perform surveillance.
Lymphoid cells (T and B cells) migrate to lymphoid organs such as the thymus, spleen, and lymph nodes, where they mature before being deployed into circulation.

What Are Cytokines? And Why Are They Important?

Cytokines are small signaling proteins that immune cells use to communicate with each other. They play a critical role in regulating immune responses, inflammation, and tissue repair.

Pro-inflammatory cytokines (e.g., IL-6, TNF-α, IFN-γ) help activate immune responses but can also contribute to chronic inflammation if uncontrolled.
Anti-inflammatory cytokines (e.g., IL-10, TGF-β) help resolve inflammation and promote healing.
Chemokines are a type of cytokine that directs immune cells to specific sites of infection or injury.

In the heart, cytokines are essential for both repairing damage and triggering inflammation. However, excessive cytokine production can lead to heart damage, arrhythmias, and heart failure1.

The Immune System in a Healthy Heart

Even in a healthy heart, there is a population of resident immune cells. But why are they there?

Macrophages have been discovered to be part of the heart since birth, maintaining tissue homeostasis2.
Studies show that cardiac macrophages play a role in electrical conduction, helping maintain heart rhythm3.
Currently, the presence of other resident immune cells in the healthy heart is still under investigation.

The Immune System in a Damaged Heart

When the heart is damaged, immune cells mobilize in response to injury, just like if you burn your skin, for example. This can be beneficial but may also drive inflammation-driven heart diseases.

Mobilization of Inflammatory Cells

Neutrophils (first responders) release enzymes that can exacerbate damage.
Macrophages and Monocytes rush to the injury site to clear dead cells.
T Cells contribute to both protection and autoimmunity.

Examples of Heart Diseases Driven by Inflammation

Myocarditis – Inflammation of the heart muscle, often driven by viral infections or autoimmune responses.
Atherosclerosis – Chronic inflammation in blood vessels leading to plaque buildup and heart attacks.
Heart Failure – Persistent immune activation contributes to fibrosis and reduced heart function.

COVID-19: A Case Study of Immune Dysregulation in the Heart

The COVID-19 pandemic has revealed how an overactive immune response can lead to heart complications. Some COVID-19 patients experience myocarditis, arrhythmias, and heart failure due to excessive cytokine release (also called a “cytokine storm”)1.

This highlights the delicate balance of immune activity, in which too little can lead to infection, while too much can cause heart damage.

Conclusion

The immune system in the heart is a double-edged sword, it is essential for protection and repair but also capable of driving disease when dysregulated. Ongoing research aims to balance immune activity to prevent excessive inflammation while promoting heart healing.

In the next blogs, I will delve deeper into the role of each immune cell in the heart, helping you better understand how this directly impacts your heart health.

References:

Lazzerini, P. E., Boutjdir, M. & Capecchi, P. L. COVID-19, Arrhythmic Risk, and Inflammation. Circulation 142, 7-9 (2020). https://doi.org:10.1161/CIRCULATIONAHA.120.047293
Honold, L. & Nahrendorf, M. Resident and Monocyte-Derived Macrophages in Cardiovascular Disease. Circulation Research 122, 113-127 (2018). https://doi.org:10.1161/CIRCRESAHA.117.311071
Hulsmans, M. et al. Macrophages Facilitate Electrical Conduction in the Heart. Cell 169, 510-522.e520 (2017). https://doi.org:10.1016/j.cell.2017.03.050