Macrophages - Cells of the Immune System

The immune system is the body’s main defence against infection. In order to function properly, the immune system must be able to detect and protect against infinite agents such as pathogens including viruses and bacteria and unhealthy or infected cells. In order to do this, various cells are required to carry out specific functions. In the article below, an overview of macrophages will be discussed including their development and functions.

What are Macrophages?

Macrophages are a type of white blood cell of the immune system that engulfs and digests cellular debris, foreign substances, pathogens and cancer cells in a process known as phagocytosis (Wikipedia Contributors, 2020). The action of phagocytosis involves the engulfment of an organism or foreign molecule into the cell. These cells also produce inflammatory molecules and mediators known as cytokines, which are involved in the signalling of other immune cells to the site of infection. Examples of these cytokines include TNF (tumour necrosis factor), IL-1, IL-6, IL-8 and IL-12 (Arango Duque & Descoteaux, 2014). They also produce antimicrobial mediators such as complement proteins and reactive oxygen species which can kill the phagocytosed pathogen (Flannagan et al., 2015).Macrophages are derived from blood monocytes, a non-specialized cell of the innate immune system in the bone marrow and differentiate into macrophages based on the stimuli at the site of infection (Hirayama et al., 2017).

Figure 1: Macrophage phagocytosis of bacteria (red) (Taken from Victoria Rees).

Macrophage Subtypes

Macrophages can be differentiated into two types, M1 and M2. M1 macrophages are pro-inflammatory and have a role in degradation of pathogens and damaged cells. They secrete pro-inflammatory cytokines and aid in the pro-inflammatory immune response (Wikipedia Contributors, 2020b). On the other hand, M2 macrophages are anti-inflammatory and are involved in tissue-repair and halting the immune response. M2 macrophages are associated with tissue repair and the production of anti-inflammatory molecules to turn the pro-inflammatory microenvironment into a more anti-inflammatory one. The types of molecules that they produce are IL-2, IL-4, TGF-beta and IL-10. In most cases the M2 macrophages aid in dampening down the immune response and prevent an excessive immune response, however, in some cases, these macrophages can lead to the formation of tumours as they stimulate the over-production of cell division (Ley, 2017).

Macrophage Functions

Macrophages recognise pathogens with the use of pattern recognition receptors which recognise specific molecules on the surface of pathogens. The type of PRR on the surface of macrophages is called a toll-like receptor (TLR). Once the macrophage has recognised a specific molecule on the surface of the pathogen such as LPS, peptidoglycan, flagellin, they phagocytose these pathogens and release several different types of pro-inflammatory molecules that are involved in recruiting different immune cells to the site of infection to aid in removing the pathogen or foreign cell (Hirayama et al., 2017). Macrophages migrate to and circulate almost every tissue and are constantly patrolling for pathogens or eliminating dead cells. Macrophages differentiate based on the tissue that they reside in. The table below conveys the various types of differentiated macrophages in tissues.

Type of Macrophage Location Function

Alveolar Macrophages

Lung Alveoli

Phagocytosis of small particles, dead cells or bacteria within respiratory system.

Kupffer Cells

Liver

Initiate immune responses in the hepatic system

Microglia

Central Nervous System

Phagocytose bacteria, dead cells within brain and CNS, control of immunity in the brain

Splenic Macrophages

Spleen Marginal Zone

Elimination of dysfunctional or old red blood cells

Osteoclasts

Bone

Bone modelling and remodelling, bone cell degradation

Adipose-tissue associated macrophages

Adipose Tissue

Metabolism, adipogenesis, adaptive thermogenesis


References

Arango Duque, G., and Descoteaux, A. (2014) Macrophage cytokines: involvement in immunity and infectious diseases. Front Immunol 5: 491.

Flannagan, R.S., Heit, B., and Heinrichs, D.E. (2015) Antimicrobial Mechanisms of Macrophages and the Immune Evasion Strategies of Staphylococcus aureus. Pathogens 4: 826-868.

Hirayama, D., Iida, T., and Nakase, H. (2017) The Phagocytic Function of Macrophage-Enforcing Innate Immunity and Tissue Homeostasis. Int J Mol Sci 19.

Ley, K. (2017) M1 Means Kill; M2 Means Heal. J Immunol 199: 2191-2193.

Wikipedia Contributors, W., (2020) Macrophages. In., pp.

15th Apr 2020 Sarah Donovan MSc

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