A healthy innate immune system is both a detective, scanning the body for potentially threatening invaders, and a first responder—thwarting pathogens and/or prompting repair. In fact, the innate immune system first appeared 750 million years ago and has been remarkably conserved throughout evolution.1 It is now understood that the innate immune system is the gatekeeper for coordinating the body’s entire immune response.2 How can dietary and lifestyle modifications work together to support the health of this sophisticated system?
Cells of the innate immune system detect the presence of many potential pathogens using germ-line encoded receptors that engage 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 cells associated with innate immune responses in the gut and liver include monocytes, macrophages, dendritic cells, natural killer and innate lymphoid cells, mast cells, neutrophils, and eosinophils.3 The innate immune system responds to a microbiologic challenge and shapes the microbiome; this, in turn, helps reshape the innate and adaptive immune systems.3
Deregulated innate immunity is increasingly common and contributes to a wide range of diseases, including intestinal diseases such as irritable bowel syndrome or other chronic inflammatory intestinal diseases;4 autoimmune diseases including type 1 diabetes and rheumatoid arthritis;5 neurodegenerative disorders such as Alzheimer’s disease, amyotrophic lateral sclerosis, Parkinson’s disease, and Huntington’s disease;6 and even chronic obstructive pulmonary disease.7
Over the last decade, a growing body of knowledge on the innate immune system has begun to be translated into clinical practice. Probiotics are emerging as potentially useful therapeutic agents.3 In the following video, IFM educator Robert Rountree, MD, outlines a number of immunomodulators he uses with patients.
Curcumin is a natural anti-inflammatory, and studies suggest that in humans, one part of the positive effects of curcumin on health could be related to its ability to enhance IL-10-mediated effects.8 IL-10 is an anti-inflammatory and immunosuppressive cytokine that is produced by both innate and adaptive immunity cells; IL-10 deregulation plays a role in a number of inflammatory diseases associated with an unhealthy innate immunity.8
A 2018 study suggests that environmental stress may induce changes in the innate immune system, causing dysfunction.9 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.9 A randomized, double-blind clinical trial found that curcumin significantly lowered atherogenic risks in patients with type 2 diabetes.10 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.11
Natural antioxidants prevent cell damage against free radicals and are critical for maintaining optimum health.12 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.12,13
Additionally, evidence suggests that exercise has a profound effect on the functioning of the immune system.14 It is generally accepted that prolonged periods of intensive exercise training can depress immunity, while regular, moderate-intensity exercise is beneficial.14 In 2018, for the first time, 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.15 Another recent study provides the first evidence to suggest that cytotoxic T cells become transiently reductive in healthy individuals following a single bout of cycling.16
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.
- 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 [published online August 11, 2017]. Crit Rev Food Sci Nutr. doi:10.1080/10408398.2017.1358139.
- Ding S, Jiang H, Fang J. Regulation of immune function by polyphenols. J Immunol Res. 2018;2018:1264074. doi:10.1155/2018/1264074.
- Cheungsamarn S, Rattanamongkolgul S, Phonrat B, Tungtrongchitr R, Jirawatnotai S. Reduction of atherogenic risk in patients with type 2 diabetes by curcuminoid extract: a randomized controlled trial. J Nutr Biochem. 2014;25(2):144-150. doi:10.1016/j.jnutbio.2013.09.013.
- Guimarães MR, Leite FR, Spolidorio LC, Kirkwood KL, Rossa C. Curcumin abrogates LPS-induced proinflammatory 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.
- Puertollano MA, Puertollano E, de Cienfuegos GÁ, de Pablo MA. Dietary antioxidants: immunity and host defense. Curr Top Med Chem. 2011;11(14):1752-1766.
- Tettamanti L, Caraffa AI, 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.
- Bartlett DB, Willis LH, Slenz 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. 2018;125(2):586-595. doi:10.1152/japplphysiol.01137.2017.