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A healthy innate immune system is both a detective, scanning the body for potentially threatening invaders, and a first responder, thwarting pathogens and prompting repair. Innate immunity first appeared 750 million years ago and has been remarkably conserved throughout evolution,1 and it is now understood to be the gatekeeper for coordinating the body’s entire immune response.2 How can diet and lifestyle modifications support the health of this critical system?
Cells of the innate immune system detect the presence of many potential pathogens using pattern recognition receptors that recognize classes of molecules common to many foreign types of bacteria, fungi, and/or viruses.3 Each organ in the body uses unique sets of cells and molecules that orchestrate regional innate immunity.1 The gut microbiota and the innate immune system have a reciprocal relationship, with any microbial disruption or dysbiosis potentially altering the innate immune response and vice versa.4,5
Deregulated innate immunity is increasingly common and has been shown to contribute to a wide range of diseases, including:
- Intestinal diseases such as irritable bowel syndrome and other chronic inflammatory intestinal diseases.6
- Autoimmune diseases, including type 1 diabetes and rheumatoid arthritis.7
- Neurodegenerative disorders such as Alzheimer’s disease, amyotrophic lateral sclerosis, Parkinson’s disease, and Huntington’s disease.8
- Chronic obstructive pulmonary disease.9
Over the last decade, a growing body of knowledge about the workings of innate immunity has been translated into clinical practice. Probiotics are emerging as potentially useful therapeutic agents. In the following video, FM educator Robert Rountree, MD, outlines a number of immunomodulators he uses with patients.
Nutritional Support and Exercise Benefits
Curcumin is a natural anti-inflammatory, and studies suggest that in humans, one aspect of the positive effects of curcumin on health could be related to its ability to enhance IL-10-mediated effects.10 IL-10 is an anti-inflammatory and immunosuppressive cytokine that is produced by both innate and adaptive immune cells; IL-10 deregulation plays a role in a number of inflammatory diseases associated with an unhealthy innate immune system.10 In addition, a 2020 review suggested that while the mechanism is unclear, phytochemicals, including curcumin, resveratrol, and sulforaphane, inhibit NLRP3 (nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3) inflammasome activity;11 this protein initiates the release of proinflammatory cytokines as part of the innate immune system and has been implicated in a wide range of chronic diseases.12
A 2018 study suggests that environmental stress may induce changes in the innate immune system, causing dysfunction.13 Nutrition, including the use of polyphenols like curcumin, may play an essential role in immunity by altering proinflammatory cytokine synthesis, immune cell regulation, and gene expression.13 In 2014, it was shown for the first time that curcumin modulates toll-like receptor (TLR) signaling in macrophages and effectively inhibits cytokine gene expression induced by TLR stimulation, indicating its therapeutic potential as a host modulatory agent in chronic infectious conditions.14 Since then, further studies have shown that curcumin has an inhibitory effect on the TLR signaling pathways, namely in TLR-2 and TLR-4 activation,15,16 suggesting its role in reducing overall inflammatory burden, particularly for autoimmune and rheumatic diseases.16,17
Natural antioxidants may reduce inflammation and oxidative stress, thereby contributing to a more robust immune system and response.15 Antioxidant nutrients such as vitamin E, vitamin C, ?-carotene, selenium, copper, iron, and zinc improve different immune functions and play a protective role in the event of an infection.18–20
Additionally, evidence suggests that exercise has a profound effect on the functioning of the immune system.21,22 It is generally accepted that prolonged periods of intensive exercise training can depress immunity, while regular, moderate-intensity exercise is beneficial.21 In 2018, research found that a high-intensity interval walking protocol in older adults with stable rheumatoid arthritis was associated with reduced disease activity, improved cardiovascular fitness, and improved innate immune functions, indicative of reduced infection risk and inflammatory potential.23 Another recent study provides evidence to suggest that cytotoxic T cells become transiently reductive (stressed) in healthy individuals following a single bout of cycling.24
What other dietary and lifestyle changes can affect immune modulation? Learn more about the physiology and pathophysiology associated with immune dysregulation and their associations with systemic disease in IFM’s Immune Advanced Practice Module (APM). The Immune APM provides clinicians with an in-depth understanding of underlying immune mechanisms and effective interventions to support and balance immune function.
- Hato T, Dagher PC. How the innate immune system senses trouble and causes trouble. Clin J Am Soc Nephrol. 2015;10(8):1459-1469. doi:10.2215/CJN.04680514.
- Du M, Chen ZJ. DNA-induced liquid phase condensation of cGAS activates innate immune signaling. Science. 2018;361(6403):704-709. doi:10.1126/science.aat1022.
- Elliott DE, Siddique SS, Weinstock JV. Innate immunity in disease. Clin Gastroenterol Hepatol. 2014;12(5):749-755. doi:10.1016/j.cgh.2014.03.007.
- Jiao Y, Wu L, Huntington ND, Zhang X. Crosstalk between gut microbiota and innate immunity and its implication in autoimmune diseases. Front Immunol. 2020;11:282. doi:10.3389/fimmu.2020.00282.
- Yue B, Luo X, Yu Z, Mani S, Wang Z, Dou W. Inflammatory bowel disease: a potential result from the collusion between gut microbiota and mucosal immune system. Microorganisms. 2019;7(10):440. doi:10.3390/microorganisms7100440.
- Kamada N, Rogler G. The innate immune system: a trigger for many chronic inflammatory intestinal diseases. Inflamm Intest Dis. 2016;1(2):70-77. doi:10.1159/000445261.
- Navegantes KC, de Souza Gomes R, Pereira PAT, Czaikoski PG, Azevedo CHM, Monteiro MC. Immune modulation of some autoimmune diseases: the critical role of macrophages and neutrophils in the innate and adaptive immunity. J Transl Med. 2017;15(1):36. doi:10.1186/s12967-017-1141-8.
- Labzin LI, Heneka MT, Latz E. Innate immunity and neurodegeneration. Annu Rev Med. 2018;69:437-449. doi:10.1146/annurev-med-050715-104343.
- Shaykhiev R, Crystal RG. Innate immunity and chronic obstructive pulmonary disease: a mini-review. Gerontology. 2013;59(6):481-489. doi:10.1159/000354173.
- Mollazadeh H, Cicero AFG, Blesso CN, Pirro M, Majeed M, Sahebkar A. Immune modulation by curcumin: the role of interleukin-10. Crit Rev Food Sci Nutr. 2019;59(1):89-101. doi:10.1080/10408398.2017.1358139.
- Olcum M, Tastan B, Ercan I, Eltutan IB, Genc S. Inhibitory effects of phytochemicals on NLRP3 inflammasome activation: a review. Phytomedicine. 2020;75:153238. doi:10.1016/j.phymed.2020.153238.
- Yang Y, Wang H, Kouadir M, Song H, Shi F. Recent advances in the mechanisms of NLRP3 inflammasome activation and its inhibitors. Cell Death Dis. 2019;10(2):128. doi:10.1038/s41419-019-1413-8.
- Ding S, Jiang H, Fang J. Regulation of immune function by polyphenols. J Immunol Res. 2018;2018:1264074. doi:10.1155/2018/1264074.
- Guimaraes MR, Leite FRM, Spolidorio LC, Kirkwood KL, Rossa C. Curcumin abrogates LPS-induced pro-inflammatory cytokines in RAW 264.7 macrophages. Evidence for novel mechanisms involving SOCS-1, -3 and p38 MAPK. Arch Oral Biol. 2013;58(10):1309-1317. doi:10.1016/j.archoralbio.2013.07.005.
- Boozari M, Butler AE, Sahebkar A. Impact of curcumin on toll-like receptors. J Cell Physiol. 2019;234(8):12471-12482. doi:10.1002/jcp.28103.
- Panaro MA, Corrado A, Benameur T, Paolo CF, Cici D, Porro C. The emerging role of curcumin in the modulation of TLR-4 signaling pathway: focus on neuroprotective and anti-rheumatic properties. Int J Mol Sci. 2020;21(7):2299. doi:10.3390/ijms21072299.
- Ebrahimzadeh A, Abbasi F, Ebrahimzadeh A, Jibril AT, Milajerdi A. Effects of curcumin supplementation on inflammatory biomarkers in patients with rheumatoid arthritis and ulcerative colitis: a systematic review and meta-analysis. Complement Ther Med. 2021;61:102773. doi:10.1016/j.ctim.2021.102773.
- Iddir M, Brito A, Dingeo G, et al. Strengthening the immune system and reducing inflammation and oxidative stress through diet and nutrition: considerations during the COVID-19 crisis. Nutrients. 2020;12(6):1562. doi:10.3390/nu12061562.
- Puertollano MA, Puertollano E, de Cienfuegos GA, de Pablo M. Dietary antioxidants: immunity and host defense. Curr Top Med Chem. 2011;11(14):1752-1766. doi:10.2174/156802611796235107.
- Tettamanti L, Caraffa A, Mastrangelo F, et al. Different signals induce mast cell inflammatory activity: inhibitory effect of Vitamin E. J Biol Regul Homeost Agents. 2018;32(1):13-19.
- Simpson RJ, Kunz H, Agha N, Graff R. Exercise and the regulation of immune functions. Prog Mol Biol Transl Sci. 2015;135:355-380. doi:10.1016/bs.pmbts.2015.08.001.
- Chastin SFM, Abaraogu U, Bourgois JG, et al. Effects of regular physical activity on the immune system, vaccination and risk of community-acquired infectious disease in the general population: systematic review and meta-analysis. Sports Med. 2021;51(8):1673-1686. doi:10.1007/s40279-021-01466-1.
- Bartlett DB, Willis LH, Slentz CA, et al. Ten weeks of high-intensity interval walk training is associated with reduced disease activity and improved innate immune function in older adults with rheumatoid arthritis: a pilot study. Arthritis Res Ther. 2018;20(1):127. doi:10.1186/s13075-018-1624-x.
- Wadley AJ, Holliday A, Morgan RG, et al. Preliminary evidence of reductive stress in human cytotoxic T cells following exercise. J Appl Physiol (1985). 2018;125(2):586-595. doi:10.1152/japplphysiol.01137.2017.