Role Of Monocytes In the Immune System

  • Vaishali S Gunjal M.Sc. Pharmaceutical Medicine, Maharashtra University of Health Science

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Introduction to monocytes

White blood cells are a crucial component of the human immune system, tasked with defending the body against harmful bacteria, viruses, fungi parasites, and other environmental toxins. Among these, monocytes are the largest type of white blood cells and are distinguished by their distinctive kidney-shaped nucleus. They play a pivotal role in both the innate and adaptive immune responses, bridging the gap between immediate defence mechanisms and long-term immunity.1

Monocyte production in the body?

Monocytes are produced in the bone marrow,2 a soft and spongy tissue found within the cavities of bones. Upon maturation, they are released into the bloodstream from the bone marrow, where they circulate in the blood for about 1-3 days and patrol for any signs of infection or inflammation in the body.

What are the types of monocytes?

  • Classical monocytes
  • Non-classical monocytes

Difference in classical monocytes and non-classical monocytes.

Classical monocytesNon-classical monocytes
  
Percentage: 80-90% of total monocytes in the bloodstreamPercentage: 5-10% of total monocytes in the bloodstream
  
CD14 Surface marker expression level: HighCD14 Surface marker expression level: Intermediate
  
CD16 Surface marker expression level: Low or No expressionCD16 Surface marker expression level: High
  
Function:
- Phagocytosis of pathogens 
- Cytokines production 
- Antigen presentation to T cells 
- Inflammatory response
Functions:
- Patrolling the blood vessels 
- Surveillance for pathogens 
- Extravasation into tissues 
- Tissue repair

Both types of Monocytes can differentiate into macrophages or dendritic cells when they migrate into tissues.

Monocyte differentiation?

Monocyte differentiation is a process where monocytes migrate into tissues when they receive chemotactic signals released by damaged or infected tissues. The process by which monocytes move through the cell walls of blood vessels and enter the tissues where they are needed is called diapedesis.3 Based on the type of signal that’s generated monocytes differentiate into another type of cell i.e. either macrophage or dendritic cell.

What is macrophage?

Macrophages are highly adaptable immune cells derived from monocytes which can perform a wide range of functions involved in fighting off infections, damaged tissue repair and immune system regulation.

There are the following types of macrophages4

  1. M1 macrophages (pro-inflammatory)
    • Involved in the initial stages of inflammation
    • Produce proinflammatory cytokines which create unfavourable conditions for the pathogens
  2. M2 Macrophages (anti-inflammatory)
    • Help resolve inflammation and promote the repair of damaged tissues and healing

Dendritic cells: the antigen presenters

Dendritic cells are found in the tissues that are in contact with the external environment for example skin, inner linings of the nose, lungs, intestines etc. They have long projections with branches called dendrites. These dendrites give them a large surface area to interact with other pathogens and immune cells.

Dendritic cells are antigen-presenting cells which capture antigens and present them to T cells, produce cytokines and play an important role in the innate and adaptive immune system.5

What are the functions of monocytes

Phagocytosis

This is a fundamental process in the immune system. The following steps are involved.

  • Recognition and attachment: Monocytes recognise the pathogen-associated molecular pattern (PAMP) on the pathogen's surface with the help of the Pattern recognition receptor (PRR) on their surface and attach themselves to the pathogen
  • Engulfment: After attaching to the pathogen, the monocytes extend their cell membrane around the pathogen, enveloping the pathogen and forming a vesicle. This vesicle is called a phagosome.
  • Phagolysosome formation: The phagosome formed earlier fuses with another organelle called a lysosome and forms a Phagolysosome
  • Enzymatic breakdown: The Phagosome contains the ingested microbe while the lysosome contains digestive enzymes. These enzymes break down the pathogen into smaller molecules
  • Waste Removal: Finally, The indigestible waste material is expelled from the monocytes through the exocytosis process

Antigen presentation

Once the pathogens are ingested, macrophages process and present Antigens (pieces of pathogens) on their surface. These antigens are important for adaptive immune response initiation. Adaptive immunity response provides long-lasting protection against pathogens but it takes time to develop after exposure to a pathogen.

Cytokine production

Macrophages produce and release a variety of signalling molecules called cytokines. 

Functions of cytokines

  1. Inflammation: Cytokines regulate inflammatory responses
  2. Cellular communication: They facilitate communication between the immune system and other systems
  3. Wound healing and tissue repair: Involved in tissue repair and regeneration.
  4. Immune regulation: Cytokines regulate immune response intensity and duration.

Tissue repair

Monocytes release cytokines and other growth factors that promote tissue healing and regeneration. They also help in tissue remodelling.

What is the clinical relevance of Monocytes

Infection indicator

Elevated levels of monocytes can indicate an ongoing infection, most commonly in chronic infections like Tuberculosis or fungal infection.

Autoimmune diseases

In autoimmune disorders such as systemic lupus erythematosus, rheumatoid arthritis and multiple sclerosis, monocytes and macrophages get dysregulated. Monitoring the dysregulated monocytes gives an insight into disease stage progression. Dysregulated macrophages can cause tissue damage through excessive inflammation further triggering autoimmune reactions.

Prognostic markers

By monitoring changes in the monocyte subset or monocyte activation state, doctors can get insight into disease progression and treatment response.

Therapeutic potential

To treat inflammatory and autoimmune disorders researchers are exploring potential pathways to modulate function and differentiation of monocytes to arrest disease progression.

  • It is essential to monitor the activation states of monocytes to understand disease progression.
  • New therapies for autoimmune diseases need to be aimed at modulating the function of monocytes/ macrophages for more effective control over disease progression.

Summary

White blood cells form a key component of the human immune system. These cells perform essential functions such as pathogen clearance, antigen presentation, cytokine production, and tissue repair. Based on any inflammation or infection trigger they receive they enter cells and differentiate into other types of cells called macrophages or dendritic cells. These macrophages and dendritic cells play a key role in various processes involved in the body's innate and adaptive immunity against various pathogens. Monitoring the state and count of Monocytes serve as key indicators for monitoring the progression stages of various autoimmune diseases and infections. Research on new treatment modalities for various diseases is being aimed at exploring the possibility of targeting monocytes to alter the disease progression.

FAQs

What are monocytes

Monocytes are the largest type of white blood cells which are an integral part of the human immune system. 

What does a high monocyte count indicate

It indicates a possible ongoing infection or inflammation and in some cases, it can also indicate autoimmune diseases, cancer

What is monocytosis

An increase in the number of monocytes is called monocytosis 

Can stress cause an increase in the number of  monocytes

Acute stress may increase monocytes.6

References 

  1. Espinoza VE, Emmady PD. Histology, Monocytes. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 [cited 2024 Jun 24]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK557618/.
  2. Furth R van, Diesselhoff-den Dulk MMC. THE KINETICS OF PROMONOCYTES AND MONOCYTES IN THE BONE MARROW. J Exp Med [Internet]. 1970 [cited 2024 Jun 24]; 132(4):813–28. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2138857/.
  3. Muller WA. Getting Leukocytes to the Site of Inflammation. Vet Pathol [Internet]. 2013 [cited 2024 Jun 24]; 50(1):7–22. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3628536/.
  4. Huang X, Li Y, Fu M, Xin H-B. Polarizing Macrophages In Vitro. In: Rousselet G, editor. Macrophages: Methods and Protocols [Internet]. New York, NY: Springer; 2018 [cited 2024 Jun 24]; p. 119–26. Available from: https://doi.org/10.1007/978-1-4939-7837-3_12.
  5. León B, López-Bravo M, Ardavín C. Monocyte-derived dendritic cells. Seminars in Immunology [Internet]. 2005 [cited 2024 Jun 24]; 17(4):313–8. Available from: https://www.sciencedirect.com/science/article/pii/S1044532305000503.
  6. Wouw M van de, Sichetti M, Long-Smith CM, Ritz NL, Moloney GM, Cusack A-M, et al. Acute stress increases monocyte levels and modulates receptor expression in healthy females. Brain, Behavior, and Immunity [Internet]. 2021 [cited 2024 Jun 24]; 94:463–8. Available from: https://www.sciencedirect.com/science/article/pii/S0889159121001070.

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Vaishali S Gunjal

M.Sc. Pharmaceutical Medicine, Maharashtra University of Health Sciences

Vaishali is a Pharmaceutical Medicine Professional currently working as a medical writer based in Leeds, UK. She has been working in the medical field for over a decade advising healthcare professionals and consumers on the proper use, benefits, and potential risks associated with pharmaceutical products used for treatment or prevention of various health conditions.

She developed a strong interest in the safe and effective use of medicines while playing a pivotal role in providing accurate and timely medical information in Pharmacovigilance- Medical Information and Regulatory roles for several years in various pharmaceutical organisations.

Through her medical writing, she aims to empower individuals with accurate health information, promote awareness, and foster informed decision-making regarding health-related issues.

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