Genetics and Mannose-Binding Lectin

The body has many ways to fight off different pathogens. Some pathogen-fighters, such as antibodies or T-cells, you may be quite familiar with, 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 is referring to plant lectins, especially those types found in grains, legumes, and nightshades.)

Quick explanation of alternative activation of the complement system:

In the body, the lectin pathway is a part of our immune system. 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, if a pathogenic bacteria has a sugar called mannose on its surface, 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, which is 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 then 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.

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

Which pathogens can activate mannose-binding lectin?

There are a variety of different 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
  • Many different gram-negative bacteria including Staphylococcus aureus
  • 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 important in apoptosis, or the way that 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 they 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 the majority of 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]
  • A lot of 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 the HIV virus, 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 times 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 that 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]

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

Genetic variants that cause mannose-binding lectin deficiency:

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Visual data overview for members:

Gene RS ID Risk Allele YOU Notes about the Risk Allele:
MBL2 rs1800450 T Lower mannose-binding lectin levels, increased risk of certain infections.
MBL2 rs709620 G Somewhat lower MBL levels
MBL2 rs1800451 T Somewhat lower MBL levels
MBL2 rs5030737 A Somewhat lower MBL levels
MASP2 rs72550870 C Decreased or deficient mannose-binding lectin protease complex. (uncommon)

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 which is 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:

If you have genetically lower MBL levels, you may be wondering 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 was shown in one study to have no impact on the MBL level. [ref]

Probiotics: Several studies have looked at different Lactobacillus species which can bind to mannose-binding lectins in an effort to prevent HIV and herpes simplex virus.[ref] Certain L. plantarum species seem to bind to mannose, but it seems that more studies need to be done on the subject.

Sunflower seedlings produce a mannose-binding type lectin.[ref]

Red algae species have been studied for binding to mannose on several types of viruses. [ref] [ref]

Again, your body has multiple ways to fight off pathogens. If you have low MBL leves, be sure that the rest of their immune system is in good shape. Zinc, vitamin D, and vitamin A are important in fighting off pathogens. Getting enough sleep, and keeping your circadian rhythm on track is also important.


Related Articles and Topics:

Genetics of Chronic Sinus Infections
Are you someone that gets sinus infections that seem to last forever? Your genes may be important here – and help to point you towards solutions that are personal for you.

Acute Respiratory Distress Syndrome (ARDS) genes
ARDS is caused by an overwhelming immune response to a virus, bacteria, or lung injury. Learn more about which of your immune system genes are involved in ARDS.

 

Originally published in June 2016. Revised and updated 10/2020.

 



Author Information:   Debbie Moon
Debbie Moon is the founder of Genetic Lifehacks. She holds a Master of Science in Biological Sciences from Clemson University and an undergraduate degree in engineering. Debbie is a science communicator who is passionate about explaining evidence-based health information. Her goal with Genetic Lifehacks is to bridge the gap between the research hidden in scientific journals and everyone's ability to use that information. To contact Debbie, visit the contact page.