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 is a part of the immune system that is not as well known.
Mannose-binding lectin, also known as mannose-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.
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. (A lot of what you read about lectins on alternative health blogs refers to plant lectins, especially those found in grains, legumes, and nightshades.)
A quick explanation of alternative activation of the complement system:
The lectin pathway is a part of our immune system in the body. It is an antibody-independent pathway, meaning the immune system can recognize new pathogens this way, not just ones that the body has already developed antibodies for.
This part of the immune response is initiated by a pathogen membrane (e.g., the cell membrane of a bacteria or envelope of a virus) containing the mannose carbohydrate.
For example, suppose a pathogenic bacteria has a sugar called mannose on its surface. In that case, the lectin pathway recognizes it, and the mannose-binding lectin, which circulates in the plasma, will bind to it.
Mannose-binding lectin, abbreviated as MBL, binds to mannose, a sugar molecule found on the surface of some pathogens. To active the immune system, though, you need a combo of MBL plus two more proteins all bound together. The MASP1 (Mannose-binding lectin-associated serine protease 1) and MASP2 proteins join together with the MBL — signaling that the 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 is a series of reactions attacking the pathogen’s cell membrane to kill the pathogen.
Which pathogens can activate mannose-binding lectin?
- Ebola and Marburg viruses (hemorrhagic fever)
- Many different gram-negative bacteria, including Staphylococcus aureus
- Infectious bronchitis virus
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]
- 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 protectively 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]
Mannose-binding lectin Genotype Report
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MLB2 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] increase the 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 —.
If you have lower MBL levels genetically, you may wonder if it is possible to raise your mannose-binding lectin level.
Thyroid: Good thyroid function is important for MBL levels.[ref] If you are hypothyroid, talk with your doctor about ways to correct your thyroid levels.
Weight: Sometimes, knowing what doesn’t work is also important. Weight loss had no impact in one study on the MBL level.[ref]
The rest of this article is for Genetic Lifehacks members only. Consider joining today to see the rest of this article.
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Originally published in June 2016. Revised and updated 10/2020.
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Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering and also an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.