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. (Much 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 activate 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
Not a member? Join here. Membership lets you see your data right in each article and also gives you access to the member’s only information in the Lifehacks sections.
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.
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.
Related Articles and Topics:
Top 10 Genes to Check in Your Genetic Raw Data
Wondering what is actually important in your genetic data? These 10 genes have important variants with a big impact on health. Check your genes (free article).
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 personalized for you.
Acute Respiratory Distress Syndrome (ARDS) genes
ARDS is caused by 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.
Areeshi, Mohammed Y., et al. “A Meta-Analysis of MBL2 Polymorphisms and Tuberculosis Risk.” Scientific Reports, vol. 6, Nov. 2016, p. 35728. PubMed, https://doi.org/10.1038/srep35728.
Brown, Elizabeth E., et al. “MBL2 and Hepatitis C Virus Infection among Injection Drug Users.” BMC Infectious Diseases, vol. 8, May 2008, p. 57. PubMed Central, https://doi.org/10.1186/1471-2334-8-57.
Chen, Mengshi, et al. “Impact of Passive Smoking, Cooking with Solid Fuel Exposure, and MBL/MASP-2 Gene Polymorphism upon Susceptibility to Tuberculosis.” International Journal of Infectious Diseases: IJID: Official Publication of the International Society for Infectious Diseases, vol. 29, Dec. 2014, pp. 1–6. PubMed, https://doi.org/10.1016/j.ijid.2014.08.010.
Chong, Yong Pil, et al. “Association of Mannose-Binding Lectin 2 Gene Polymorphisms with Persistent Staphylococcus Aureus Bacteremia.” PLoS ONE, vol. 9, no. 3, Mar. 2014, p. e89139. PubMed Central, https://doi.org/10.1371/journal.pone.0089139.
Complement Deficiencies | Immune Deficiency Foundation. https://primaryimmune.org/about-primary-immunodeficiencies/specific-disease-types/complement-deficiencies/. Accessed 13 May 2022.
Høyem, P. H., et al. “The Effect of Weight Loss on Serum Mannose-Binding Lectin Levels.” Clinical and Developmental Immunology, vol. 2012, Nov. 2012, p. e354894. www.hindawi.com, https://doi.org/10.1155/2012/354894.
Https://Limo.Libis.Be/Primo-Explore/Fulldisplay?Docid=LIRIAS1759532&context=L&vid=Lirias&search_scope=Lirias&tab=default_tab&lang=en_US&fromSitemap=1. https://limo.libis.be/primo-explore/fulldisplay?docid=LIRIAS1759532&context=L&vid=Lirias&search_scope=Lirias&tab=default_tab&lang=en_US&fromSitemap=1. Accessed 13 May 2022.
Kjærup, Rikke M., et al. “Adjuvant Effects of Mannose-Binding Lectin Ligands on the Immune Response to Infectious Bronchitis Vaccine in Chickens with High or Low Serum Mannose-Binding Lectin Concentrations.” Immunobiology, vol. 219, no. 4, Apr. 2014, pp. 263–74. PubMed Central, https://doi.org/10.1016/j.imbio.2013.10.013.
Levy, Emily R., et al. “Evaluation of Mannose Binding Lectin Gene Variants in Pediatric Influenza Virus-Related Critical Illness.” Frontiers in Immunology, vol. 10, 2019, p. 1005. PubMed, https://doi.org/10.3389/fimmu.2019.01005.
Lin, Yong, et al. “Impact of Mannose-Binding Lectin 2 Polymorphism on the Risk of Hepatocellular Carcinoma: A Case-Control Study in Chinese Han Population.” Journal of Epidemiology, vol. 25, no. 5, May 2015, pp. 387–91. PubMed Central, https://doi.org/10.2188/jea.JE20140194.
Liu, Lei, and Bo Ning. “The Role of MBL2 Gene Polymorphism in Sepsis Incidence.” International Journal of Clinical and Experimental Pathology, vol. 8, no. 11, 2015, pp. 15123–27.
Longhi, Luca, et al. “Mannose-Binding Lectin Is Expressed after Clinical and Experimental Traumatic Brain Injury and Its Deletion Is Protective.” Critical Care Medicine, vol. 42, no. 8, Aug. 2014, pp. 1910–18. PubMed, https://doi.org/10.1097/CCM.0000000000000399.
Michelow, Ian C., et al. “High-Dose Mannose-Binding Lectin Therapy for Ebola Virus Infection.” The Journal of Infectious Diseases, vol. 203, no. 2, Jan. 2011, pp. 175–79. PubMed Central, https://doi.org/10.1093/infdis/jiq025.
Ogden, C. A., et al. “C1q and Mannose Binding Lectin Engagement of Cell Surface Calreticulin and CD91 Initiates Macropinocytosis and Uptake of Apoptotic Cells.” The Journal of Experimental Medicine, vol. 194, no. 6, Sept. 2001, pp. 781–95. PubMed, https://doi.org/10.1084/jem.194.6.781.
Orsini, Franca, et al. “Mannose-Binding Lectin Drives Platelet Inflammatory Phenotype and Vascular Damage After Cerebral Ischemia in Mice via IL (Interleukin)-1α.” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 38, no. 11, Nov. 2018, pp. 2678–90. ahajournals.org (Atypon), https://doi.org/10.1161/ATVBAHA.118.311058.
Rashidi, Elahe, et al. “Mannose-Binding Lectin Deficiency in Patients with a History of Recurrent Infections.” Iranian Journal of Allergy, Asthma and Immunology, Jan. 2016, pp. 69–74. ijaai.tums.ac.ir, https://ijaai.tums.ac.ir/index.php/ijaai/article/view/628.
Regente, Mariana, et al. “A Sunflower Lectin with Antifungal Properties and Putative Medical Mycology Applications.” Current Microbiology, vol. 69, no. 1, July 2014, pp. 88–95. PubMed, https://doi.org/10.1007/s00284-014-0558-z.
Riis, Anne Lene Dalkjær, et al. “Thyroid Hormone Increases Mannan-Binding Lectin Levels.” European Journal of Endocrinology, vol. 153, no. 5, Nov. 2005, pp. 643–49. eje.bioscientifica.com, https://doi.org/10.1530/eje.1.02013.
Rs1800450 – SNPedia. https://snpedia.com/index.php/Rs1800450. Accessed 13 May 2022.
Rs72550870 – SNPedia. https://snpedia.com/index.php/Rs72550870. Accessed 13 May 2022.
Ruskamp, Jopje M., et al. “Mannose-Binding Lectin and Upper Respiratory Tract Infections in Children and Adolescents: A Review.” Archives of Otolaryngology–Head & Neck Surgery, vol. 132, no. 5, May 2006, pp. 482–86. Silverchair, https://doi.org/10.1001/archotol.132.5.482.
Tong, Xiang, et al. “Association between the Mannose-Binding Lectin (MBL)-2 Gene Variants and Serum MBL with Pulmonary Tuberculosis: An Update Meta-Analysis and Systematic Review.” Microbial Pathogenesis, vol. 132, July 2019, pp. 374–80. PubMed, https://doi.org/10.1016/j.micpath.2019.04.023.
Tu, Xinyi, et al. “Functional Polymorphisms of the CCL2 and MBL Genes Cumulatively Increase Susceptibility to Severe Acute Respiratory Syndrome Coronavirus Infection.” The Journal of Infection, vol. 71, no. 1, July 2015, pp. 101–09. PubMed, https://doi.org/10.1016/j.jinf.2015.03.006.
UpToDate. https://www.uptodate.com/contents/mannose-binding-lectin? Accessed 13 May 2022.
Zhang, Nana, et al. “Association of Levels of Mannose-Binding Lectin and the MBL2 Gene with Type 2 Diabetes and Diabetic Nephropathy.” PLoS ONE, vol. 8, no. 12, Dec. 2013, p. e83059. PubMed Central, https://doi.org/10.1371/journal.pone.0083059.
Ziółkowska, Natasza E., and Alexander Wlodawer. “Structural Studies of Algal Lectins with Anti-HIV Activity.” Acta Biochimica Polonica, vol. 53, no. 4, 2006, pp. 617–26.
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.