Implications of Inflammatory States on Dysfunctional Immune Responses in Aging and Obesity

Overview

Journal Front Aging

Specialty Geriatrics

Date 2022 Jul 13

PMID 35822048

Authors

Alyssa L Thomas

Pablo C Alarcon

Senad Divanovic

Claire A Chougnet

David A Hildeman

Maria E Moreno-Fernandez

Affiliations

Soon will be listed here.

Abstract

Aging and obesity are two conditions characterized by chronic, low-grade inflammation. While both conditions are also associated with dysfunctional immune responses, the shared and distinct underlying mechanisms are just starting to be uncovered. In fact, recent findings have suggested that the effects of obesity on the immune system can be thought of as a state of accelerated aging. Here we propose that chronic, low-grade inflammation seen in obesity and aging is complex, affects multiple cell types, and results in an altered basal immune state. In aging, part of this altered state is the emergence of regulatory immune populations that lead to further immune dysfunction in an attempt to reduce chronic inflammation. While in obesity, part of the altered state is the effect of expanding adipose tissue on immune cell function. Thus, in this review, we compare, and contrast altered immune states in aging and obesity and discuss their potential contribution to a shared clinical problem- decreased vaccine responsiveness.

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References

Leonardi G, Accardi G, Monastero R, Nicoletti F, Libra M . Ageing: from inflammation to cancer. Immun Ageing. 2018; 15:1. PMC: 5775596. DOI: 10.1186/s12979-017-0112-5. View

Defuria J, Belkina A, Jagannathan-Bogdan M, Snyder-Cappione J, Carr J, Nersesova Y . B cells promote inflammation in obesity and type 2 diabetes through regulation of T-cell function and an inflammatory cytokine profile. Proc Natl Acad Sci U S A. 2013; 110(13):5133-8. PMC: 3612635. DOI: 10.1073/pnas.1215840110. View

Vasanthakumar A, Chisanga D, Blume J, Gloury R, Britt K, Henstridge D . Sex-specific adipose tissue imprinting of regulatory T cells. Nature. 2020; 579(7800):581-585. PMC: 7241647. DOI: 10.1038/s41586-020-2040-3. View

Winer D, Winer S, Shen L, Wadia P, Yantha J, Paltser G . B cells promote insulin resistance through modulation of T cells and production of pathogenic IgG antibodies. Nat Med. 2011; 17(5):610-7. PMC: 3270885. DOI: 10.1038/nm.2353. View

Friedrich K, Sommer M, Strobel S, Thrum S, Bluher M, Wagner U . Perturbation of the Monocyte Compartment in Human Obesity. Front Immunol. 2019; 10:1874. PMC: 6694869. DOI: 10.3389/fimmu.2019.01874. View

Frasca D, Blomberg B, Paganelli R . Aging, Obesity, and Inflammatory Age-Related Diseases. Front Immunol. 2017; 8:1745. PMC: 5725402. DOI: 10.3389/fimmu.2017.01745. View

Sadeghi H, Schnelle J, Thoma J, Nishanian P, Fahey J . Phenotypic and functional characteristics of circulating monocytes of elderly persons. Exp Gerontol. 2000; 34(8):959-70. DOI: 10.1016/s0531-5565(99)00065-0. View

Ishikawa A, Wada T, Nishimura S, Ito T, Okekawa A, Onogi Y . Estrogen regulates sex-specific localization of regulatory T cells in adipose tissue of obese female mice. PLoS One. 2020; 15(4):e0230885. PMC: 7117686. DOI: 10.1371/journal.pone.0230885. View

Reuman P, Kubilis P, Hurni W, Brown L, Nalin D . The effect of age and weight on the response to formalin inactivated, alum-adjuvanted hepatitis A vaccine in healthy adults. Vaccine. 1997; 15(10):1157-61. DOI: 10.1016/s0264-410x(96)00310-6. View

10.

Kim Y, Choi B, Cheon H, Do M . B cell activation factor (BAFF) is a novel adipokine that links obesity and inflammation. Exp Mol Med. 2009; 41(3):208-16. PMC: 2679246. DOI: 10.3858/emm.2009.41.3.024. View

11.

Russo L, Lumeng C . Properties and functions of adipose tissue macrophages in obesity. Immunology. 2018; 155(4):407-417. PMC: 6230999. DOI: 10.1111/imm.13002. View

12.

Pang W, Price E, Sahoo D, Beerman I, Maloney W, Rossi D . Human bone marrow hematopoietic stem cells are increased in frequency and myeloid-biased with age. Proc Natl Acad Sci U S A. 2011; 108(50):20012-7. PMC: 3250139. DOI: 10.1073/pnas.1116110108. View

13.

Wong C, Smith C, Sakamoto K, Kaminski N, Koff J, Goldstein D . Aging Impairs Alveolar Macrophage Phagocytosis and Increases Influenza-Induced Mortality in Mice. J Immunol. 2017; 199(3):1060-1068. PMC: 5557035. DOI: 10.4049/jimmunol.1700397. View

14.

Grant R, Dixit V . Adipose tissue as an immunological organ. Obesity (Silver Spring). 2015; 23(3):512-8. PMC: 4340740. DOI: 10.1002/oby.21003. View

15.

Chan C, Harley I, Pfluger P, Trompette A, Stankiewicz T, Allen J . A BAFF/APRIL axis regulates obesogenic diet-driven weight gain. Nat Commun. 2021; 12(1):2911. PMC: 8131685. DOI: 10.1038/s41467-021-23084-1. View

16.

Feuerer M, Herrero L, Cipolletta D, Naaz A, Wong J, Nayer A . Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Nat Med. 2009; 15(8):930-9. PMC: 3115752. DOI: 10.1038/nm.2002. View

17.

Jin R, Kaneko H, Suzuki H, Arai T, Teramoto T, Fukao T . Age-related changes in BAFF and APRIL profiles and upregulation of BAFF and APRIL expression in patients with primary antibody deficiency. Int J Mol Med. 2008; 21(2):233-8. View

18.

Skurk T, Alberti-Huber C, Herder C, Hauner H . Relationship between adipocyte size and adipokine expression and secretion. J Clin Endocrinol Metab. 2006; 92(3):1023-33. DOI: 10.1210/jc.2006-1055. View

19.

Monti D, Ostan R, Borelli V, Castellani G, Franceschi C . Inflammaging and human longevity in the omics era. Mech Ageing Dev. 2017; 165(Pt B):129-138. DOI: 10.1016/j.mad.2016.12.008. View

20.

Narasaraju T, Yang E, Perumal Samy R, Ng H, Poh W, Liew A . Excessive neutrophils and neutrophil extracellular traps contribute to acute lung injury of influenza pneumonitis. Am J Pathol. 2011; 179(1):199-210. PMC: 3123873. DOI: 10.1016/j.ajpath.2011.03.013. View