Overview

Monocytes are a type of white blood cell also referred to as a leukocyte essential to the immune system's function. They are found within blood and tissues and have various crucial roles including fighting off and clearing infections and recruiting other white blood cells to aid recovery and prevent infections. Monocytosis is a condition in which there is an increased concentration of monocytes found circulating in the abnormal blood. The normal range of monocytes in the average healthy adult is approximately  0.2 – 0.8 × 10⁹/L (subject to gender and age) and the World Health Organization states persistent monocytosis tends to be above 1 × 10⁹/L whereby monocytes count for around 10% of leukocytes found in the bloodstream.^1,2 This article will explore the characteristics of monocytes in the body of healthy and infected individuals as well as the treatment and management of monocytosis. 

Understanding monocytes 

Monocytes originate in the bone marrow and are differentiated from stem cells. Following the myeloid stem cell lineage these stem cells further differentiate into monocytes with the potential to differentiate into macrophages or dendritic cells all of which are important for our immune system.⁸ The human immune system has two key components: the innate immune system which is the first responder to foreign pathogens and infection.⁹ Then we have the second component known as the adaptive immune system which helps develop immune memory via antigen production.¹⁰ Monocytes,  responsibilities focus more on the innate immune system but are important to both innate and adaptive systems as these must work together to clear and detect an infection.

When a monocyte differentiates into a macrophage the key role is performing phagocytosis. Phagocytosis is the process in which a macrophage engulfs a pathogen and destroys it. They are also important for engulfing and destroying dead and dying cells within the body to clear up debris.³ Another key role of monocytes that have differentiated into macrophages is the secretion of cytokines.⁴ This occurs under inflammatory conditions in which the release of cytokines can help control and regulate the immune response. 

Monocytes can also differentiate into dendritic cells, which can also perform phagocytosis, but their key role is to present antigens to T-cells found in the lymph nodes. This allows T-cells to be activated and neutralise pathogens that have entered the body.⁵ These are the linkers between the innate and adaptive immune systems. 

Causes

Monocytosis indicates that an immune response is ongoing within the body. There are three common causes:

• Infection: An infection caused by a pathogen(bacteria, virus, parasite or fungi)¹¹
• Chronic inflammatory Conditions: Termed as autoimmune disorders, including rheumatoid arthritis and lupus¹²
• Hematologic (Blood) disorders: Conditions primarily affecting the bloodstream such as leukaemia¹⁴

Mechanisms

One key mechanism that elevates monocyte count includes an immune response to infection. When infection occurs, the immune system can have an inflammatory response.⁷ During this time the innate immune system is activated and as monocytes are a crucial component of our innate immune system levels increase to try and clear the pathogen causing the infection. A second mechanism that can result in an increased monocyte count is bone marrow stimulation. Bone marrow stimulation occurs as a result of infection or injury,¹¹ and can lead to an increase in the release of cytokines, hence elevated levels of monocytes.⁶

Monocytosis and pathogenic infections

As previously mentioned, monocytes circulate in the bloodstream. When a pathogen enters the body this triggers the innate immune response. From here, there is an increase in monocytes because the immune system has been activated. Processes activated include monocytes migrating to the site of infection. Here macrophages are activated to engulf and destroy the pathogen (phagocytosis) at the site of infection.¹⁵ Monocytes in the bloodstream can also differentiate into dendritic cells which will present the pathogen antigen and migrate to the lymph nodes which activates T-cells.¹⁶ This then allows the immune system to produce antibodies against that particular pathogen that has invaded the body. In order to tackle the invading pathogen monocyte production is thus increased and released from the bone marrow for both specific (antibody production - lymph nodes) and non-specific immune responses (phagocytosis - infection site). 

There are many pathogens that can cause monocytosis. Some examples of infections that are associated with monocytosis include:

• Bacterial infections: Tuberculosis, SARS-CoV2, Listeriosis²¹
• Viral Infections : Epstein-barr Virus, Cytomegalovirus, Measles²⁰
• Parasitic Infections: Malaria, Visceral Leishmaniasis^18,19
• Fungal infections: Candidiasis, Cryptococcosis, Aspergillosis¹⁷

Symptoms and diagnosis

Monocytosis as a condition itself is generally asymptomatic. The symptoms are usually related to the underlying infection or health condition of the individual. There are a few general signs that can be looked for but again these are usually a result of the underlying health issue. This may include symptoms such as:

• Fever
• Fatigue
• Body and muscle aches
• Changes to the skin, e.g., Rash

Diagnosing a patient with monocytosis involves a blood test in which a complete blood count (CBC), as well as differential blood count, will display the different measures of both red blood cells and white blood cell types. The main cell types that indicate monocytosis are monocytes and their differentiated cell types which include the level of both dendritic cells and macrophages. If monocytosis is identified, then additional tests such as blood cultures and imaging studies can be used to identify the cause.¹ Identifying the cause of monocytosis is important because this will determine the treatment used to treat the individual.

Treatment and management

The key to treating monocytosis is to address the underlying infection. This is particularly important when the infection is pathogenic as some treatments for certain pathogens cannot be used on others. For example, antibiotics cannot be used to tackle a viral infection that has led to monocytosis because antibiotics only target bacteria. It is also important because overuse and misuse of antimicrobial treatments can result in antimicrobial resistance, which means the treatment will no longer be effective against the pathogen.²² Treatments for different pathogens include:

1. Bacterial Infection: Antibiotics
2. Viral Infection: Antivirals
3. Fungal Infection: Antifungals
4. Parasitic Infection: Antiparasitics

Once the diagnosis and the course of treatment are finished, the patient can be monitored and followed up. This may involve regular blood tests to monitor monocyte levels, in particular, if they have decreased back to a normal range or if further treatment is required. Infections that are not pathogenic might result from chronic conditions such as inflammatory bowel disease or rheumatoid arthritis.¹³ In these cases, treatment would be focused on reducing inflammation as it is the inflammatory response from the body causing elevated monocyte levels. 

Prevention and lifestyle considerations

Due to the different causes of monocytosis, there are different ways to manage and prevent the condition. To prevent monocytosis associated with pathogenic infections key strategies would include following good hygiene practices, getting routine vaccinations and following health and sanitation protocols that allow you to avoid exposure to known pathogens. For example, healthcare workers wear the correct PPE when around patients. Lifestyle considerations are also important in preventing the body from becoming inflamed and managing underlying health conditions that may lead to monocytosis. Considerations include having a balanced diet, getting regular exercise, getting good sleep, and trying to manage stress levels. When the body gets stressed, it could lead to inflammation, resulting in monocytosis.  

Summary

Overall, monocytosis is important because it indicates that an immune response has been activated in our body. This response suggests an underlying health issue, such as a pathogenic infection or chronic inflammation. Understanding the relationship between monocytosis and infection is crucial because, even though the body is trying to fight the infection, antimicrobial treatment may still be required. Fortunately, diagnostics like blood tests allow us to monitor monocyte levels and determine whether immune responses are still being activated. This monitoring can demonstrate the body's ability to tackle disease and regulate monocyte levels or indicate that further treatment is needed. Finally, if you have an underlying condition causing chronic inflammation or concerns about monocytes and infection, it is important to seek medical advice. Diagnosing monocytosis is straightforward, and early detection can lead to faster treatment and better health outcomes.