In people with selenium deficiency (variously defined as serum selenium status below 60 mcg/L or 70 mcg/L), the responses of the innate and adaptive immune systems may be impaired.
Selenium deficiency can lead to an immune-incompetence that is associated with increased susceptibility to infections [Avery & Hoffmann 2018; Hiffler et al. 2020].
In cell culture models, in rodent models, in livestock and poultry studies, and in human studies, researchers have found evidence that adequate levels of dietary selenium and the efficient incorporation of selenium into selenoproteins are important for immune system function [Avery & Hoffmann 2018].
Studies of selenium supplementation to boost immunity against pathogens have not provided entirely clear-cut results; however, selenium and selenoproteins do play a role in regulating immune cell functions. Dysregulation of these immune cell processes can lead to inflammation and immune-related diseases [Avery & Hoffmann 2018].
Selenium Supplementation for Low Selenium-Status Individuals
Selenium supplementation, for the most part, is immuno-stimulatory; this effect has been measured by several different parameters [reviewed by Avery & Hoffmann 2018]. The effects of the selenium supplementation seem to depend on the baseline selenium status:
- The strongest beneficial effects have been seen when the supplementation has raised selenium levels from inadequate (under 70 mcg/L) to adequate (above 100 mcg/L).
- The benefits of supplementation have been less clear in studies in which adequate selenium levels (generally, between 100 mcg/L and 170 mcg/L) have been raised to supra-nutritional levels (defined as above 170 mcg/L).
Overview of the Innate and Adaptive Immune Systems
The human immune system comprises two systems: the innate immune system and the adaptive immune system. The innate immune system is present from birth; it provides an immediate response to invading pathogens (viruses, bacteria, fungi).
The innate immune system uses phagocytes to engulf and destroy invading microorganisms. The most prominent types of phagocytes are monocytes, macrophages, neutrophils, tissue dendritic cells and mast cells. Phagocytes deal with harmful invaders by inducing inflammatory responses and by engulfing pathogens and destroying pathogens by exposing them to oxidative stress from reactive oxygen species.
White blood cells known as Natural Killer cells are a part of the innate immune system. The NK cells play an important role in the limiting and controlling of microbial infections. They kill cells infected by viruses, and they also kill many tumor cells.
Following the immediate innate immune response, in cases of more severe infections, the body activates the adaptive immune system. The adaptive immune system responds with B and T lymphocytes (white blood cells in the blood, lymph, and lymphoid tissue). The B lymphocytes produce the antibodies that neutralize specific antigens (antigens = toxins that have provoked an immune response).
The T lymphocytes have three different forms and roles in responding to the presence of infected cells in the body:
- The helper T cells secrete chemical messengers (cytokines) that which set in motion the development of B cells into antibody-producing cells.
- The regulatory T cells control the extent of immune reactions.
- The cytotoxic T cells bind to and kill infected cells and cancer cells.
Bridging the gap between the innate and adaptive immune systems are the cytokines, the signaling molecules that are secreted when pathogens are encountered by cells. Cytokines are the messengers that tell the two immune systems what types of responses to mobilize. An inflammatory reaction is one of the immune responses that cytokines elicit. As we know from Covid-19, too many cytokines can have a negative effect, can produce a “cytokine storm.”
Selenium and the Innate Immune System
Selenium status impacts innate immune cell functions in various ways:
- Selenium levels affect the macrophages’ inflammatory signaling capacity and anti-pathogen activities.
- Selenium levels and selenoproteins regulate macrophage migration and phagocytosis functions in the macrophages.
- Less information is available regarding selenium levels and neutrophil function. One study has demonstrated that increased selenium intake may protect neutrophils from endogenous oxidative stress.
- Dietary selenium intake levels impact NK cells both directly and indirectly.
- In mice, selenium supplementation increased the cytotoxic functions of NK cells.
Selenium and the Adaptive Immune System
Selenium intake and status affect the activation and functions of B cells and T cells.
- Higher selenium levels have a positive effect on the proliferation and differentiation of CD4+ T helper cells.
- The effect of selenium status on cytotoxic CD8+ T cells has not been investigated as much: a mouse study has shown that cytotoxic T cells from aged mice (24 months old) had enhanced proliferation when the mice were treated with selenium supplementation.
- Mouse models have shown roles for selenoproteins in antibody production.
Immune Responses to Pathogens Affected by Selenium
Sufficient selenium status is required for innate and adaptive immune responses against infections to be effective.
Selenium and Bacterial Infections
- Selenium is one of many nutrients that has been implicated in the severity and progression of tuberculosis caused by the bacterium Mycobacterium tuberculosis.
- Pulmonary TB patients have lower selenium status compared to healthy controls.
Selenium and Viral Infections
The antioxidant properties of some selenoproteins are associated with the enhancement of anti-viral immunity. Moreover, some selenoproteins that are not necessarily antioxidant enzymes, e.g. Selenoprotein K, can also play key roles in protecting against viruses.
- Selenium status has been associated with the extent to which chronic hepatitis C virus influences oxidative stress levels in humans.
- Low selenium status can lead to greater virulence of certain viruses, e.g. the coxsackie virus B3 and the influenza viruses.
- Selenium supplementation to increase the selenium status of individuals with low selenium intake and status may be an effective initiative to enhance individual responses to vaccines.
- Adequate selenium status helps to protect against vulnerability to viral pathogens, e.g. polio and influenza pathogens.
Selenium Status and HIV Infections
The role of selenium in anti-viral immunity has been most investigated in patients with HIV infections, which are infections that directly impair immune response.
- Low selenium intake is associated with HIV prevalence.
- Low selenium intake is associated with reduced CD4+ T cell counts in HIV-positive patients.
- Cohort studies have shown an association between selenium deficiency and progression to AIDS-related mortality.
- Randomized controlled trials have shown that selenium supplementation minimizes hospitalizations and diarrheal morbidity and improves CD4+ T cell counts.
- Selenium-deficient HIV-positive patients tend to have low plasma selenium levels, low red blood cell selenium levels, diminished activity by the antioxidant selenoprotein glutathione peroxidase, and reduced bioavailability of selenium in the heart muscle tissue
Conclusion: U-Shaped Relationship between Selenium Status and Health
- Nearly all tissues are affected by changes in selenium status and changes in selenoprotein expression.
- Selenium status below a certain level (60-70 mcg/L) is associated with reduced adaptive immunity and exacerbated inflammation [Avery & Hoffmann 2018].
- Selenium status below a certain level (60-70 mcg/L) is associated with prevalence and severity of infections, e.g. HIV and TB [Avery & Hoffmann 2018].
- Selenium status below a certain level (60-70 mcg/L) is associated with more severe signs and symptoms of heart failure, with worse New York Heart Association functional class, with poorer exercise capacity (6-min walking test), and with poorer quality of life [Bomer 2019].
- Optimal selenium status (100-170 mcg/L) is associated with enhanced T cell proliferation, enhanced NK cell activity, and improved innate immune system function [Avery & Hoffmann 2018].
- Optimal selenium status (100-170 mcg/L) is associated with a stronger response to vaccines and a more robust immune defense against pathogens [Avery & Hoffmann 2018].
- Optimal selenium status (100-170 mcg/L) is associated with less severe inflammation in lung tissue and intestine tissue [Avery & Hoffmann 2018].
Sources
Avery JC, Hoffmann PR. Selenium, Selenoproteins, and Immunity. Nutrients. 2018 Sep 1;10(9):1203.
Bomer N, Grote Beverborg N, Hoes MF, Streng KW, Vermeer M, Dokter MM, IJmker J, Anker SD, Cleland JGF, Hillege HL, Lang CC, Ng LL, Samani NJ, Tromp J, van Veldhuisen DJ, Touw DJ, Voors AA, van der Meer P. Selenium and outcome in heart failure. Eur J Heart Fail. 2020 Aug;22(8):1415-1423.
Guillin OM, Vindry C, Ohlmann T, Chavatte L. Selenium, Selenoproteins and Viral Infection. Nutrients. 2019 Sep 4;11(9):2101.
Hiffler L, Rakotoambinina B. Selenium and RNA Virus Interactions: Potential Implications for SARS-CoV-2 Infection (COVID-19). Front Nutr. 2020 Sep 4;7:164.
The information presented in this review article is not intended as medical advice and should not be used as such.
15 April 2021