Genetics and Mannose-Binding Lectin

The body has many ways to fight off different pathogens. You may be quite familiar with some pathogen-fighters, such as antibodies or T-cells, but the lectin pathway and mannose-binding lectin is a part of the immune system that is not as well known.

Mannose-binding lectin, also known as mannose-binding protein or mannan binding protein, is involved in the body’s innate defense against infections. Find out how genetic variants in this system increase your susceptibility to specific pathogens.

Table of Contents

Mannose-binding Lectin and the Immune System

First, let me give some background information on lectins and the innate immune system.

Lectin is a general term for a protein that binds to a carbohydrate, and lectins are found in the body as part of the immune system and as cell receptors. (Much of what you read about lectins on alternative health blogs refers to plant lectins, especially those found in grains, legumes, and nightshades. That isn’t what we are talking about here…)

A quick explanation of “alternative activation of the complement system”:

The lectin pathway is part of our immune system in the body. It is an antibody-independent pathway, which means that the immune system can use it to recognize new pathogens, not just those for which the body has already developed antibodies.

This part of the immune response is initiated by a pathogen membrane (such as the cell membrane of a bacterium or the envelope of a virus) that contains the carbohydrate mannose.

Mannose-binding lectin, abbreviated as MBL, binds to mannose, a sugar molecule found on the surface of some pathogens, such as Streptococcus pneumoniae or the hepatitis C virus.

To activate the immune system, though, you need a combination of mannose binding lectin (MBL) plus two more proteins that bind to it. The MASP1 (Mannose-binding lectin-associated serine protease 1) and MASP2 proteins join together with MBL, signaling that the viral or bacterial cell they are bound to is a pathogen that needs to be removed.

This combination of MBL, MASP1, and MASP2 activates the part of the immune system called the complement system. The complement system initiates a series of reactions that attack the pathogen’s cell membrane to kill the pathogen.

Recap: Mannose-binding lectin is part of the body’s immune response to pathogens like certain bacteria and viruses.

Which pathogens can activate mannose-binding lectin?

There are various bacteria, viruses, and microorganisms that can activate the complement system through MBL. These pathogens include:[ref][ref]

Ebola and Marburg viruses (hemorrhagic fever)
SARS-CoV
HIV
Influenza
Quite a few gram-negative bacteria, including Staphylococcus aureus (staph)
Infectious bronchitis virus
SARS-CoV-2[ref]

Mannose-binding lectin and apoptosis:

In addition to its role in pathogen recognition, mannose-binding lectin is also essential in apoptosis, or how the body gets rid of cellular debris.[ref]

Genetics and Mannose Binding Lectin:

Genetically, some people either produce less effective MBL than the rest of the population or produce less MBL, depending on the variant.[ref]

Resiliency:
Our immune system has lots of backup ways of taking care of pathogens; thus, a deficiency of MBL is not always a problem. Often someone will not know that they have it.

Studies show the following for MBL deficiency:

MBL deficiency can be a bigger problem for someone with a compromised immune system.[ref]
Children with MBL deficiency have more frequent ear infections and/or upper respiratory infections.[ref] Not all studies show this, but most studies indicate a statistically higher rate of respiratory infections in kids.[ref]
There can be an increased risk of abscesses, meningitis, and sepsis with low MBL levels.[ref]
Decreased MBL is linked to increased odd of recurrent sinus infections.[ref]
Many studies have looked at the role of MBL in HIV infections, as mannose-binding lectin can be important for preventing AIDS. MBL can bind to the surface of HIV, so it is being studied to determine if increased MBL affects the rate of progression of HIV.

Good and bad:
It isn’t as cut-and-dry as MBL deficiency being ‘bad’. There are pros and cons associated with the amount of MBL in the body. Often a higher immune response is great for pathogens, but there are tradeoffs with inflammatory processes in the body.

A 2014 mouse study found that MBL is involved in traumatic brain injuries; mice with MBL deficits had fewer sensorimotor deficits than mice with normal MBL.[ref]
Other studies show that mannose-binding lectin may be involved in inflammation in blood cells, promoting inflammation there.[ref]
Higher levels of mannose-binding lectin are linked with a greater risk of diabetic kidney disease (variants that cause low levels of MBL are protective against kidney disease in diabetes).[ref]

Not uncommon!
MBL deficiency is not all that rare. Some studies estimate that about 5% of people have undetectable levels of mannose-binding lectin, while another 30% have very low levels. It varies a bit by population group.[ref]

Recap: Genetic variants can decrease or eliminate MBL. This decrease could cause increased susceptibility to infections.

Autoimmune diseases and low MBL:

SLE (systemic lupus erythematosus) and RA (rheumatoid arthritis) are more common in people with low mannose-binding lectin. Genetic variants in the MBL gene are also linked to an increased relative risk of Sjögren’s syndrome.[ref]

Covid and mannose-binding lectin:

I mentioned above that MBL can bind to the SARS-CoV-2 virus and activate the immune response. Specifically, mannose-binding lectin can activate certain aspects of the immune response, such as natural killer cells, MBL also modulates T cells and keeps the immune response under control.[ref]

Other causes of decreased mannose binding lectin:

Genetic variants are the most frequent reason for low MBL levels, but there are a few other causes:

Altered hormones, such as thyroid hormone or pituitary hormones can also impact MBL levels, independent of genetic variants.
Hypothyroidism is linked to lower levels of MBL, while hyperthyroidism is associated with higher MBL levels. [ref]
Hypopituitary hormones are also linked to significantly lower levels of MBL.[ref]

Mannose-binding lectin Genotype Report:

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MBL2 gene: codes for mannose-binding lectin, which activates the complement system.

Check your genetic data for rs1800450 (23andMe v4, v5; AncestryDNA):

C/C: typical
C/T: likely to have lower mannose-binding lectin protein complex levels[ref]
T/T: mannose-binding protein deficiency[ref]; greater risk of staph infections and MRSA[ref][ref]; increased risk of tuberculosis[ref]

Members: Your genotype for rs1800450 is —.

Check your genetic data for rs7096206 (23andMe v4; AncestryDNA):

C/C: typical
C/G: somewhat lower MBL levels
G/G: Lower MBL, increased risk of liver cancer[ref], increased risk of tuberculosis in nonsmokers[ref]

Members: Your genotype for rs7096206 is —.

Check your genetic data for rs1800451 (AncestryDNA)

C/C: typical
C/T: somewhat lower MBL
T/T: somewhat lower MBL, increased risk of TB[ref]

Members: Your genotype for rs1800451 is —.

Check your genetic data for rs5030737 (23andMe v4, v5; AncestryDNA)

G/G: typical
A/G: somewhat lower MBL
A/A: lower MBL levels[ref]

Members: Your genotype for rs5030737 is —.

MASP2 gene: The gene MASP2 codes for mannose-binding protein-associated serine protease 2 involved in the MBL pathway.

Check your genetic data for rs72550870 (23andMe v4, v5; AncestryDNA)

T/T: typical
C/T: decreased mannose-binding lectin protease complex.
C/C: MASP2 deficiency (uncommon)[ref][ref]

Members: Your genotype for rs72550870 is —.

Lifehacks: Natural solutions for low mannose-binding lectin

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