Exercise immunology: Future directions

Abstract

Several decades of research in the area of exercise immunology have shown that the immune system is highly responsive to acute and chronic exercise training. Moderate exercise bouts enhance immunosurveillance and when repeated over time mediate multiple health benefits. Most of the studies prior to 2010 relied on a few targeted outcomes related to immune function. During the past decade, technologic advances have created opportunities for a multi-omics and systems biology approach to exercise immunology. This article provides an overview of metabolomics, lipidomics, and proteomics as they pertain to exercise immunology, with a focus on immunometabolism. This review also summarizes how the composition and diversity of the gut microbiota can be influenced by exercise, with applications to human health and immunity. Exercise-induced improvements in immune function may play a critical role in countering immunosenescence and the development of chronic diseases, and emerging omics technologies will more clearly define the underlying mechanisms. This review summarizes what is currently known regarding a multi-omics approach to exercise immunology and provides future directions for investigators.

Keywords: Exercise; Immunology; Lipidomics; Metabolomics; Proteomics.

Graphical abstract

Fig. 1

Immune, stress, and multi-omics approaches to measuring the physiologic stress resulting from prolonged and intensive exercise. NK = natural killer; PUFA = Polyunsaturated fatty acid.

Fig. 2

Mean fold increases for 26 metabolites in a select, targeted panel that represents global metabolite increases induced by prolonged, intensive exercise. This select panel includes metabolites primarily from the lipid super pathway.

Fig. 3

Exercise-induced increases in oxylipins (ratio values, immediate postexercise/pre-exercise, represented by the red line) for n = 45 oxylipins and the substrate fatty acids arachidonic acid (ARA), EPA, and DHA. Blood samples were collected from 20 athletes cycling 75 km in an overnight fasted state. 5-iso PGF2αVI = (8ß)-5,9α,11α-trihydroxy-prostadienoic acid; 5-oxo-ETE = 5-oxo-eicosatetraenoic acid; 12-HHTrE = 12-hydroxy-heptadecatrienoic acid; 20-COOH-AA = 20-carboxy arachidonic acid; DiHDPA = dihydroxy-docosapentaenoic acid; DiHETrE = dihydroxy-eicosatrienoic acid; DiHOME = dihydroxy-octadecenoic acid; DHA = docosahexaenoic acid; EPA = eicosapentaenoic acid; EpOME = epoxy-octadecenoic acid; HDoHE = hydroxy-docosahexaenoic acid; HEPE = hydroxy-eicosapentaenoic acid; HETE = hydroxy-eicosatetraenoic acid; HETrE = hydroxy-eicosatrienoic acid; HODE = hydroxy-octadecadienoic acid; HOTrE = hydroxy-octadecatrienoic acid; oxo-ODE = oxooctadecadienoic acid; PGDM = prostaglandin D2 metabolite; PGFM = 13,14-dihydro-15-keto-prostaglandin F2α; TxB2 = thromboxane B2.

Fig. 4

STRING protein–protein interactions using immune-related proteins (n = 29, primary) increasing immediately after running or cycling 2.5 h at 70% VO_2max. Dried blood-spot samples were collected pre- and postexercise in athletes (n = 10) and analyzed using global proteomics procedures. ACTB = actin, cytoplasmic 1; ACTBL2 = beta-actin-like protein 2; ACTN1 = alpha-actinin-1; C1QC = complement C1q subcomponent subunit C; C1S = complement C1s subcomponent; C7 = complement component C7; CAMP = cathelicidin antimicrobial peptide; CENPE = centromere-associated protein E; CP = ceruloplasmin; DEFA1B = defensin, alpha 1B; ELANE = neutrophil elastase; FLNA = filamin-A; FLOT2 = flotillin-2; GSTP1 = glutathione S-transferase P; GYPA = glycophorin-A; HP = haptoglobin; ITGB3 = integrin beta-3; LYZ = lysozyme C; PF4 = platelet factor 4; PFN1 = profilin-1; PPBP = platelet basic protein; PRDX1 = peroxiredoxin-1; PSM = proteasome subunits, types A1, A1, A6, B2, B3, B4, C3; S100A8 = protein S100-A8; S100A12 = protein S100-A12; SERPINB1 = leukocyte elastase inhibitor; STRING, Search Tool for the Retrieval of Interacting Genes/Proteins; TLN1 = talin-1; VO_2max = maximal oxygen consumption; VTN = vitronectin.