For anyone who has studied biology, macrophages have most likely been on your reading list at one point or another. Microglia on the other hand are less likely to feature on your undergraduate syllabus (or else I’m older than I like to admit!). In this post, we introduce both cell types and point out their similarities and differences.

Macrophages – The Big Eaters

It might sound funny but the word macrophage actually means ‘big eater’ in Greek (frommakrós” meaning ‘big’ and “phageín” meaning ‘to eat’.). And given the role of macrophages, they really couldn’t be named more appropriately. Their major function is to phagocytose and digest microbes, tumor cells, foreign agents, cellular debris, and just about anything else that doesn’t resemble a healthy host cell. They are found in almost all bodily tissues, where they act as sentinels, patrolling for pathogens and other potential threats by moving around in an amoeboid-like fashion. Macrophages are white blood cells that originate from the myeloid progenitor lineage of multipotent hematopoietic stem cells.

Multitasking Macrophages

Although macrophages are best known for phagocytosis, it is not all they do. They play important roles in both innate and adaptive immunity through the recruitment of other immune cells e.g., lymphocytes. Along with B cells and dendritic cells, they belong to an army of professional antigen-presenting cells (APCs), presenting pathogen-derived peptides to helper T cells to stimulate appropriate anti-pathogen immune responses.

An efficient immune system hinges upon a delicate balance of pro- and anti-inflammatory responses. While inflammation is an important part of our defense against pathogens, uncontrolled inflammation can be just as dangerous as the foreign invader, and inflammation must also be downplayed after an infection in order to promote wound healing. Macrophages release anti-inflammatory cytokines e.g., IL-10 and TGF-β to downplay inflammation. Although it’s not black and white, pro-inflammatory macrophages are generally considered to be M1 macrophages, while M2 macrophages are those with anti-inflammatory effects.

Microglia Are Big Eaters Too!

Yes, really! Microglia are indeed eaters, but they are specialized ones that are only found in the brain and spinal cord (i.e., the central nervous system or CNS). Microglia make up as much as 15 % of the brain’s total cell density and constitute the brain’s main line of defense.

Microglial cells scavenge the brain tissue for pathogens, plaques, damaged neurons and synapses, and any other changes that might damage the CNS. Given the delicate nature of the brain and its surroundings, even the slightest pathological or homeostatic change must be detected and acted upon. This is made possible by the action of unique potassium channels in the cell membrane of microglial cells, allowing them to respond to the most minute fluctuations in extracellular potassium.

Thanks to the blood brain barrier, the CNS is not usually invaded directly by pathogens or pathogen-derived molecules present in the blood. However, some pathogens, e.g., the yeast Cryptococcus neoformans and the bacteria Streptococcus pneumonia (both of which cause meningitis), do cross the blood brain barrier, and in such cases, microglia act as rapid responders to decrease inflammation and destroy the pathogens before neural damage occurs. Microglia also produce a number of growth and repair factors to promote repair of damaged CNS tissue.

Microglia in Action

Under ‘normal’ or physiological conditions, microglia exist in a so-called ‘resting state’, with a small cell body. However, they are far from resting because they are highly alert at all times, managing to scan the entire brain every few hours via their processes, which continuously send out and retract protrusions.

Because the brain is virtually devoid of antibodies (most antibodies are too large to cross the blood brain barrier), microglia must be able to rapidly recognize and engulf foreign bodies, and act as antigen-presenting cells to activate T-cells. Upon activation by a stimulus e.g., a pathogen or a damaged neuron, microglia undergo a transformation from the resting state to an activated state (with elaborate processes), eventually transitioning to a phagocytic state if necessary (i.e., depending on the type and level of threat). During the phagocytic state, microglia look like other macrophages with an amoeboid-like appearance, expressing pro-inflammatory cytokines e.g., TNF- α.

So How Do They Compare?

In many ways, macrophages and microglia are similar. They guard their territories and phagocytose pathogens and other offenders, and they produce an array of pro- and anti-inflammatory cytokines and growth factors, all depending on the exact stimulus that led to their activation. Yet they differ in many ways, as outlined in the table below.

Macrophages Microglia
Lineage The myeloid progenitor lineage of multipotent hematopoietic stem cell. Macrophages specifically originate from blood monocytes that leave the bloodstream to differentiate in different tissues e.g., Kupffer cells in the liver. Yolk sac-derived myeloid precursor cells. Enter the brain during early embryonic development and continue to migrate and mature in the first weeks after birth.
Time taken to remove cellular and pathogen-derived debris Maximum of two weeks Days to many weeks
Activation trigger Primed macrophages are activated by stimulus e.g., bacterial LPS. Likely involves ‘on’ and ‘off’ signals that inform each microglial about the status of the brain tissue in their territory.

‘On’ signals might include abnormal molecules or high concentrations of physiologically normal molecules.

‘Off’ signals might include the removal of certain molecules released during normal CNS activity.

First line of defense? Macrophages are not the first line of defense. Microglia are the first line of defense in the CNS.
Calcium “waves” Macrophages do not exhibit responses to fluctuations in calcium levels. Microglia exhibit calcium wave responses, and this is a hallmark of glial cell function in the CNS.
Expressed biomarkers CD14, CD163, CD16, CCR2 ApoE/variants, hP2RY-12, TREM2, hGPR34, CXCR3 and CD11b/c

That was a sweeping introduction to macrophages vs. microglia. Given their implication in Alzheimer’s and other neurodegenerative diseases (as discussed in a previous article), it is no surprise that microglia are the subject of intense research efforts directed towards the development of personalized medicines. For high-quality microglia for your research, do check out Tempo Bioscience’s custom microglia service.

Do you work with microglia? We’ve love to hear your experiences!


Article by Karen O’Hanlon Cohrt PhD. Contact Karen at karen@tempobioscience.com. 

Karen O’Hanlon Cohrt is a Science Writer with a PhD in biotechnology from Maynooth University, Ireland (2011). After her PhD,  Karen moved to Denmark and held postdoctoral positions in mycology and later in human cell cycle regulation, before moving to the world of drug discovery. Her broad research background provides the technical know-how to support scientists in diverse areas, and this in combination with her passion for writing helps her to keep abreast of exciting research developments as they unfold. Follow Karen on Twitter @KarenOHCohrt. Karen has been a science writer since 2014; you can find her other work on her portfolio.