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Annual Review of Nutrition

Volume 42, 2022

Obesity Dysregulates the Immune Response to Influenza Infection and Vaccination Through Metabolic and Inflammatory Mechanisms

Abstract

The COVID-19 pandemic demonstrates that obesity alone, independent of comorbidities, is a significant risk factor for severe outcomes from infection. This susceptibility mirrors a similar pattern with influenza infection; that is, obesity is a unique risk factor for increased morbidity and mortality. Therefore, it is critical to understand how obesity contributes to a reduced ability to respond to respiratory viral infections. Herein, we discuss human and animal studies with influenza infection and vaccination that show obesity impairs immunity. We cover several key mechanisms for the dysfunction. These mechanisms include systemic and cellular level changes that dysregulate immune cell metabolism and function in addition to how obesity promotes deficiencies in metabolites that control the resolution of inflammation and infection. Finally, we discuss major gaps in knowledge, particularly as they pertain to diet and mechanisms, which will drive future efforts to improve outcomes in response to respiratory viral infections in an increasingly obese population.

Keyword(s): immunity, influenza, metabolism, obesity, specialized proresolving mediators
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/content/journals/10.1146/annurev-nutr-062320-115937
2022-08-22
2024-04-25
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Literature Cited

  1. 1.
    Abdulnour RE, Sham HP, Douda DN, Colas RA, Dalli J et al. 2016. Aspirin-triggered resolvin D1 is produced during self-resolving gram-negative bacterial pneumonia and regulates host immune responses for the resolution of lung inflammation. Mucosal Immunol 9:1278–87
     [Google Scholar]
  2. 2.
    Alwarawrah Y, Nichols AG, Green WD, Eisner W, Kiernan K et al. 2020. Targeting T-cell oxidative metabolism to improve influenza survival in a mouse model of obesity. Int. J. Obes. 44:2419–29
     [Google Scholar]
  3. 3.
    Andrade FB, Gualberto A, Rezende C, Percegoni N, Gameiro J, Hottz ED. 2021. The weight of obesity in immunity from influenza to COVID-19. Front. Cell. Infect. Microbiol. 11:638852
     [Google Scholar]
  4. 4.
    Asher A, Tintle NL, Myers M, Lockshon L, Bacareza H, Harris WS. 2021. Blood omega-3 fatty acids and death from COVID-19: a pilot study. Prostaglandins Leukot. Essent. Fatty Acids 166:102250
     [Google Scholar]
  5. 5.
    Bashir S, Sharma Y, Jairajpuri D, Rashid F, Nematullah M, Khan F. 2019. Alteration of adipose tissue immune cell milieu towards the suppression of inflammation in high fat diet fed mice by flaxseed oil supplementation. PLOS ONE 14:e0223070
     [Google Scholar]
  6. 6.
    Bello-Chavolla OY, Bahena-Lopez JP, Antonio-Villa NE, Vargas-Vazquez A, Gonzalez-Diaz A et al. 2020. Predicting mortality due to SARS-CoV-2: a mechanistic score relating obesity and diabetes to COVID-19 outcomes in Mexico. J. Clin. Endocrinol. Metab. 105:8dgaa346
     [Google Scholar]
  7. 7.
    Bertola A, Ciucci T, Rousseau D, Bourlier V, Duffaut C et al. 2012. Identification of adipose tissue dendritic cells correlated with obesity-associated insulin-resistance and inducing Th17 responses in mice and patients. Diabetes 61:2238–47
     [Google Scholar]
  8. 8.
    Bhatraju PK, Ghassemieh BJ, Nichols M, Kim R, Jerome KR et al. 2020. Covid-19 in critically ill patients in the Seattle region—case series. N. Engl. J. Med. 382:2012–22
     [Google Scholar]
  9. 9.
    Bouvier NM, Palese P. 2008. The biology of influenza viruses. Vaccine 26:Suppl. 4D49–53
     [Google Scholar]
  10. 10.
    Carbo R, Guarner V. 2010. Insulin effect on glucose transport in thymocytes and splenocytes from rats with metabolic syndrome. Diabetol. Metab. Syndr. 2:64
     [Google Scholar]
  11. 11.
    Casas R, Sacanella E, Urpi-Sarda M, Corella D, Castaner O et al. 2016. Long-term immunomodulatory effects of a Mediterranean diet in adults at high risk of cardiovascular disease in the PREvención con DIeta MEDiterránea (PREDIMED) randomized controlled trial. J. Nutr. 146:1684–93
     [Google Scholar]
  12. 12.
    Castoldi A, Naffah de Souza C, Camara NO, Moraes-Vieira PM. 2015. The macrophage switch in obesity development. Front. Immunol. 6:637
     [Google Scholar]
  13. 13.
    Chandra RK. 1980. Cell-mediated immunity in genetically obese (C57BL/6J ob/ob) mice. Am. J. Clin. Nutr. 33:13–16
     [Google Scholar]
  14. 14.
    Chen Q, Zheng Z, Zhang C, Zhang X, Wu H et al. 2020. Clinical characteristics of 145 patients with corona virus disease 2019 (COVID-19) in Taizhou, Zhejiang, China. Infection 48:543–51
     [Google Scholar]
  15. 15.
    Chen Y, Tian J, Tian X, Tang X, Rui K et al. 2014. Adipose tissue dendritic cells enhances inflammation by prompting the generation of Th17 cells. PLOS ONE 9:e92450
     [Google Scholar]
  16. 16.
    Chiang N, de la Rosa X, Libreros S, Pan H, Dreyfuss JM, Serhan CN. 2021. Cysteinyl-specialized proresolving mediators link resolution of infectious inflammation and tissue regeneration via TRAF3 activation. PNAS 118:e2013374118
     [Google Scholar]
  17. 17.
    Cho WJ, Lee DK, Lee SY, Sohn SH, Park HL et al. 2016. Diet-induced obesity reduces the production of influenza vaccine-induced antibodies via impaired macrophage function. Acta Virol. 60:298–306
     [Google Scholar]
  18. 18.
    Clària J, Dalli J, Yacoubian S, Gao F, Serhan CN. 2012. Resolvin D1 and resolvin D2 govern local inflammatory tone in obese fat. J. Immunol. 189:2597–605
     [Google Scholar]
  19. 19.
    Costanzo AE, Taylor KR, Dutt S, Han PP, Fujioka K, Jameson JM. 2015. Obesity impairs γδ T cell homeostasis and antiviral function in humans. PLOS ONE 10:e0120918
     [Google Scholar]
  20. 20.
    Crouch MJ, Kosaraju R, Guesdon W, Armstrong M, Reisdorph N et al. 2018. Frontline science: a reduction in DHA-derived mediators in male obesity contributes toward defects in select B cell subsets and circulating antibody. J. Leukoc. Biol. 106:241–57
     [Google Scholar]
  21. 21.
    Crouse AB, Grimes T, Li P, Might M, Ovalle F, Shalev A. 2020. Metformin use is associated with reduced mortality in a diverse population with COVID-19 and diabetes. Front. Endocrinol. 11:600439
     [Google Scholar]
  22. 22.
    Darling AL, Ahmadi KR, Ward KA, Harvey NC, Couto Alves A et al. 2020. Vitamin D status, body mass index, ethnicity and COVID-19: initial analysis of the first-reported UK Biobank COVID-19 positive cases (n 580) compared with negative controls (n 723). medRxiv:2020.04.29.20084277
  23. 23.
    Deng J, Chen Q, Chen Z, Liang K, Gao X et al. 2021. The metabolic hormone leptin promotes the function of TFH cells and supports vaccine responses. Nat. Commun. 12:3073
     [Google Scholar]
  24. 24.
    Deng T, Lyon CJ, Minze LJ, Lin J, Zou J et al. 2013. Class II major histocompatibility complex plays an essential role in obesity-induced adipose inflammation. Cell Metab 17:411–22
     [Google Scholar]
  25. 25.
    Diaz A, Romero M, Vazquez T, Lechner S, Blomberg BB, Frasca D. 2017. Metformin improves in vivo and in vitro B cell function in individuals with obesity and type-2 diabetes. Vaccine 35:2694–700
     [Google Scholar]
  26. 26.
    Eliakim A, Swindt C, Zaldivar F, Casali P, Cooper DM. 2006. Reduced tetanus antibody titers in overweight children. Autoimmunity 39:137–41
     [Google Scholar]
  27. 27.
    Farooqi IS, Matarese G, Lord GM, Keogh JM, Lawrence E et al. 2002. Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. J. Clin. Investig. 110:1093–103
     [Google Scholar]
  28. 28.
    Fezeu L, Julia C, Henegar A, Bitu J, Hu FB et al. 2011. Obesity is associated with higher risk of intensive care unit admission and death in influenza A (H1N1) patients: a systematic review and meta-analysis. Obes. Rev. 12:653–59
     [Google Scholar]
  29. 29.
    Fischer HJ, Sie C, Schumann E, Witte AK, Dressel R et al. 2017. The insulin receptor plays a critical role in T cell function and adaptive immunity. J. Immunol. 198:1910–20
     [Google Scholar]
  30. 30.
    Frasca D, Blomberg BB. 2017. Adipose tissue inflammation induces B cell inflammation and decreases B cell function in aging. Front. Immunol. 8:1003
     [Google Scholar]
  31. 31.
    Frasca D, Diaz A, Romero M, Thaller S, Blomberg BB. 2019. Metabolic requirements of human pro-inflammatory B cells in aging and obesity. PLOS ONE 14:e0219545
     [Google Scholar]
  32. 32.
    Frasca D, Reidy L, Cray C, Diaz A, Romero M et al. 2021. Influence of obesity on serum levels of SARS-CoV-2-specific antibodies in COVID-19 patients. PLOS ONE 16:e0245424
     [Google Scholar]
  33. 33.
    Fujisaka S, Usui I, Bukhari A, Ikutani M, Oya T et al. 2009. Regulatory mechanisms for adipose tissue M1 and M2 macrophages in diet-induced obese mice. Diabetes 58:2574–82
     [Google Scholar]
  34. 34.
    Gerriets VA, Danzaki K, Kishton RJ, Eisner W, Nichols AG et al. 2016. Leptin directly promotes T-cell glycolytic metabolism to drive effector T-cell differentiation in a mouse model of autoimmunity. Eur. J. Immunol. 46:1970–83
     [Google Scholar]
  35. 35.
    Gerriets VA, Rathmell JC. 2012. Metabolic pathways in T cell fate and function. Trends Immunol. 33:168–73
     [Google Scholar]
  36. 36.
    Gordon-Larsen P, French JE, Moustaid-Moussa N, Voruganti VS, Mayer-Davis EJ et al. 2021. Synergizing mouse and human studies to understand the heterogeneity of obesity. Adv Nutr 12:2023–34
     [Google Scholar]
  37. 37.
    Green WD, Al-Shaer AE, Shi Q, Gowdy KM, MacIver NJ et al. 2021. Metabolic and functional impairment of CD8+ T cells from the lungs of influenza-infected obese mice. J. Leukoc. Biol. 111:147–59
     [Google Scholar]
  38. 38.
    Gurzell EA, Teague H, Duriancik D, Clinthorne J, Harris M et al. 2015. Marine fish oils are not equivalent with respect to B-cell membrane organization and activation. J. Nutr. Biochem. 26:369–77
     [Google Scholar]
  39. 39.
    Gurzell EA, Teague H, Harris M, Clinthorne J, Shaikh SR, Fenton JI. 2012. DHA-enriched fish oil targets B cell lipid microdomains and enhances ex vivo and in vivo B cell function. J. Leukoc Biol. 93:463–70
     [Google Scholar]
  40. 40.
    Hagan T, Cortese M, Rouphael N, Boudreau C, Linde C et al. 2019. Antibiotics-driven gut microbiome perturbation alters immunity to vaccines in humans. Cell 178:1313–28.e13
     [Google Scholar]
  41. 41.
    Harrington WN, Kackos CM, Webby RJ. 2021. The evolution and future of influenza pandemic preparedness. Exp. Mol. Med. 53:737–49
     [Google Scholar]
  42. 42.
    Helderman JH, Strom TB. 1978. Specific insulin binding site on T and B lymphocytes as a marker of cell activation. Nature 274:62–63
     [Google Scholar]
  43. 43.
    Ho FK, Celis-Morales CA, Gray SR, Katikireddi SV, Niedzwiedz CL et al. 2020. Modifiable and non-modifiable risk factors for COVID-19: results from UK Biobank. medRxiv:2020.04.28.20083295
  44. 44.
    Honce R, Schultz-Cherry S. 2019. Impact of obesity on influenza A virus pathogenesis, immune response, and evolution. Front. Immunol. 10:1071
     [Google Scholar]
  45. 45.
    Hulme KD, Noye EC, Short KR, Labzin LI. 2021. Dysregulated inflammation during obesity: driving disease severity in influenza virus and SARS-CoV-2 infections. Front. Immunol. 12:770066
     [Google Scholar]
  46. 46.
    Ibrahim S, Lowe JR, Bramante CT, Shah S, Klatt NR et al. 2021. Metformin and Covid-19: focused review of mechanisms and current literature suggesting benefit. Front. Endocrinol. 12:587801
     [Google Scholar]
  47. 47.
    Jacobs SR, Herman CE, Maciver NJ, Wofford JA, Wieman HL et al. 2008. Glucose uptake is limiting in T cell activation and requires CD28-mediated Akt-dependent and independent pathways. J. Immunol. 180:4476–86
     [Google Scholar]
  48. 48.
    Karlsson EA, Hertz T, Johnson C, Mehle A, Krammer F, Schultz-Cherry S. 2016. Obesity outweighs protection conferred by adjuvanted influenza vaccination. mBio 7:4e01144–16
     [Google Scholar]
  49. 49.
    Karlsson EA, Milner JJ, Green WD, Rebeles J, Schultz-Cherry S, Beck MA. 2019. Influence of obesity on the response to influenza infection and vaccination. Mechanisms and Manifestations of Obesity in Lung Diseases RA Johnston, BT Suratt 227–59 Cambridge, MA: Academic
     [Google Scholar]
  50. 50.
    Karlsson EA, Sheridan PA, Beck MA. 2010. Diet-induced obesity impairs the T cell memory response to influenza virus infection. J. Immunol. 184:3127–33
     [Google Scholar]
  51. 51.
    Karlsson EA, Sheridan PA, Beck MA. 2010. Diet-induced obesity in mice reduces the maintenance of influenza-specific CD8+ memory T cells. J. Nutr. 140:1691–97
     [Google Scholar]
  52. 52.
    Kiernan K, MacIver NJ. 2020. The role of the adipokine leptin in immune cell function in health and disease. Front. Immunol. 11:622468
     [Google Scholar]
  53. 53.
    Kim N, Lannan KL, Thatcher TH, Pollock SJ, Woeller CF, Phipps RP. 2018. Lipoxin B4 enhances human memory B cell antibody production via upregulating cyclooxygenase-2 expression. J. Immunol. 201:3343–51
     [Google Scholar]
  54. 54.
    Kim SY, Lim JH, Choi SW, Kim M, Kim ST et al. 2010. Preferential effects of leptin on CD4 T cells in central and peripheral immune system are critically linked to the expression of leptin receptor. Biochem. Biophys. Res. Commun. 394:562–68
     [Google Scholar]
  55. 55.
    Kosaraju R, Guesdon W, Crouch MJ, Teague HL, Sullivan EM et al. 2017. B cell activity is impaired in human and mouse obesity and is responsive to an essential fatty acid upon murine influenza infection. J. Immunol. 198:124738–52
     [Google Scholar]
  56. 56.
    Lam QL, Wang S, Ko OK, Kincade PW, Lu L. 2010. Leptin signaling maintains B-cell homeostasis via induction of Bcl-2 and Cyclin D1. PNAS 107:13812–17
     [Google Scholar]
  57. 57.
    Lamichhane PP, Samarasinghe AE. 2019. The role of innate leukocytes during influenza virus infection. J. Immunol. Res. 2019:8028725
     [Google Scholar]
  58. 58.
    Lee B-C, Lee J 2014. Cellular and molecular players in adipose tissue inflammation in the development of obesity-induced insulin resistance. Biochim. Biophys. Acta Mol. Basis Dis. 1842:446–62
     [Google Scholar]
  59. 59.
    Lee YS, Olefsky J. 2021. Chronic tissue inflammation and metabolic disease. Genes Dev. 35:307–28
     [Google Scholar]
  60. 60.
    Leiria LO, Wang CH, Lynes MD, Yang K, Shamsi F et al. 2019. 12-Lipoxygenase regulates cold adaptation and glucose metabolism by producing the omega-3 lipid 12-HEPE from brown fat. Cell Metab. 30:768–83.e7
     [Google Scholar]
  61. 61.
    Li P, Oh DY, Bandyopadhyay G, Lagakos WS, Talukdar S et al. 2015. LTB4 promotes insulin resistance in obese mice by acting on macrophages, hepatocytes and myocytes. Nat. Med. 21:239–47
     [Google Scholar]
  62. 62.
    Li T, Zhang Y, Gong C, Wang J, Liu B et al. 2020. Prevalence of malnutrition and analysis of related factors in elderly patients with COVID-19 in Wuhan, China. Eur. J. Clin. Nutr. 74:871–75
     [Google Scholar]
  63. 63.
    Liao X, Chen H, Wang B, Li Z, Zhang Z et al. 2020. Critical care for severe COVID-19: a population-based study from a province with low case-fatality rate in China. medRxiv:2020.03.22.20041277
  64. 64.
    Liu M, He P, Liu HG, Wang XJ, Li FJ et al. 2020.. [ Clinical characteristics of 30 medical workers infected with new coronavirus pneumonia. ]. Zhonghua Jie He He Hu Xi Za Zhi [Chin. J. Tuberc. Respir. Dis.] 43209–14 in Chinese )
     [Google Scholar]
  65. 65.
    Lopez-Vicario C, Titos E, Walker ME, Alcaraz-Quiles J, Casulleras M et al. 2019. Leukocytes from obese individuals exhibit an impaired SPM signature. FASEB J 33:7072–83
     [Google Scholar]
  66. 66.
    Lord GM, Matarese G, Howard JK, Baker RJ, Bloom SR, Lechler RI. 1998. Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression. Nature 394:897–901
     [Google Scholar]
  67. 67.
    Louie JK, Acosta M, Samuel MC, Schechter R, Vugia DJ et al. 2011. A novel risk factor for a novel virus: obesity and 2009 pandemic influenza A (H1N1). Clin. Infect. Dis. 52:301–12
     [Google Scholar]
  68. 68.
    Macintyre AN, Gerriets VA, Nichols AG, Michalek RD, Rudolph MC et al. 2014. The glucose transporter Glut1 is selectively essential for CD4 T cell activation and effector function. Cell Metab. 20:61–72
     [Google Scholar]
  69. 69.
    MacIver NJ, Michalek RD, Rathmell JC. 2013. Metabolic regulation of T lymphocytes. Annu. Rev. Immunol. 31:259–83
     [Google Scholar]
  70. 70.
    Mandel MA, Mahmoud AA. 1978. Impairment of cell-mediated immunity in mutation diabetic mice (db/db). J. Immunol. 120:1375–77
     [Google Scholar]
  71. 71.
    Marelli-Berg FM, Fu H, Mauro C. 2012. Molecular mechanisms of metabolic reprogramming in proliferating cells: implications for T-cell-mediated immunity. Immunology 136:363–69
     [Google Scholar]
  72. 72.
    Miao T, Huang B, He N, Sun L, Du G et al. 2020. Decreased plasma maresin 1 concentration is associated with diabetic foot ulcer. Mediators Inflamm. 2020:4539035
     [Google Scholar]
  73. 73.
    Michalek RD, Gerriets VA, Jacobs SR, Macintyre AN, MacIver NJ et al. 2011. Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets. J. Immunol. 186:3299–303
     [Google Scholar]
  74. 74.
    Milner JJ, Sheridan PA, Karlsson EA, Schultz-Cherry S, Shi Q, Beck MA. 2013. Diet-induced obese mice exhibit altered heterologous immunity during a secondary 2009 pandemic H1N1 infection. J. Immunol. 191:2474–85
     [Google Scholar]
  75. 75.
    Montague CT, Farooqi IS, Whitehead JP, Soos MA, Rau H et al. 1997. Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature 387:903–8
     [Google Scholar]
  76. 76.
    Morita M, Kuba K, Ichikawa A, Nakayama M, Katahira J et al. 2013. The lipid mediator protectin D1 inhibits influenza virus replication and improves severe influenza. Cell 153:112–25
     [Google Scholar]
  77. 77.
    Mothe-Satney I, Filloux C, Amghar H, Pons C, Bourlier V et al. 2012. Adipocytes secrete leukotrienes: contribution to obesity-associated inflammation and insulin resistance in mice. Diabetes 61:2311–19
     [Google Scholar]
  78. 78.
    Neidich SD, Green WD, Rebeles J, Karlsson EA, Schultz-Cherry S et al. 2017. Increased risk of influenza among vaccinated adults who are obese. Int. J. Obes. 41:1324–30
     [Google Scholar]
  79. 79.
    Neuhofer A, Zeyda M, Mascher D, Itariu BK, Murano I et al. 2013. Impaired local production of proresolving lipid mediators in obesity and 17-HDHA as a potential treatment for obesity-associated inflammation. Diabetes 62:1945–56
     [Google Scholar]
  80. 80.
    Nishimura S, Manabe I, Nagasaki M, Eto K, Yamashita H et al. 2009. CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity. Nat. Med. 15:914–20
     [Google Scholar]
  81. 81.
    Nishimura S, Manabe I, Takaki S, Nagasaki M, Otsu M et al. 2013. Adipose natural regulatory B cells negatively control adipose tissue inflammation. Cell Metab 18:759–66
     [Google Scholar]
  82. 82.
    O'Shea D, Corrigan M, Dunne MR, Jackson R, Woods C et al. 2013. Changes in human dendritic cell number and function in severe obesity may contribute to increased susceptibility to viral infection. Int. J. Obes. 37:1510–13
     [Google Scholar]
  83. 83.
    O'Sullivan D, van der Windt GJ, Huang SC, Curtis JD, Chang CH et al. 2014. Memory CD8+ T cells use cell-intrinsic lipolysis to support the metabolic programming necessary for development. Immunity 41:75–88
     [Google Scholar]
  84. 84.
    Osterholm MT, Kelley NS, Sommer A, Belongia EA. 2012. Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis. Lancet Infect. Dis. 12:36–44
     [Google Scholar]
  85. 85.
    Ozata M, Ozdemir IC, Licinio J. 1999. Human leptin deficiency caused by a missense mutation: multiple endocrine defects, decreased sympathetic tone, and immune system dysfunction indicate new targets for leptin action, greater central than peripheral resistance to the effects of leptin, and spontaneous correction of leptin-mediated defects. J. Clin. Endocrinol. Metab. 84:3686–95
     [Google Scholar]
  86. 86.
    Paich HA, Sheridan PA, Handy J, Karlsson EA, Schultz-Cherry S et al. 2013. Overweight and obese adult humans have a defective cellular immune response to pandemic H1N1 influenza A virus. Obesity 21:2377–86
     [Google Scholar]
  87. 87.
    Painter SD, Ovsyannikova IG, Poland GA. 2015. The weight of obesity on the human immune response to vaccination. Vaccine 33:4422–29
     [Google Scholar]
  88. 88.
    Pal A, Al-Shaer AE, Guesdon W, Torres MJ, Armstrong M et al. 2020. Resolvin E1 derived from eicosapentaenoic acid prevents hyperinsulinemia and hyperglycemia in a host genetic manner. FASEB J. 34:810640–56
     [Google Scholar]
  89. 89.
    Pal A, Gowdy KM, Oestreich KJ, Beck M, Shaikh SR. 2020. Obesity-driven deficiencies of specialized pro-resolving mediators may drive adverse outcomes during SARS-CoV-2 infection. Front. Immunol. 11:1997
     [Google Scholar]
  90. 90.
    Palmas F, Clarke J, Colas RA, Gomez EA, Keogh A et al. 2021. Dysregulated plasma lipid mediator profiles in critically ill COVID-19 patients. PLOS ONE 16:e0256226
     [Google Scholar]
  91. 91.
    Park HL, Shim SH, Lee EY, Cho W, Park S et al. 2014. Obesity-induced chronic inflammation is associated with the reduced efficacy of influenza vaccine. Hum. Vaccin. Immunother. 10:1181–86
     [Google Scholar]
  92. 92.
    Pascoal LB, Bombassaro B, Ramalho AF, Coope A, Moura RF et al. 2017. Resolvin RvD2 reduces hypothalamic inflammation and rescues mice from diet-induced obesity. J. Neuroinflammation 14:5
     [Google Scholar]
  93. 93.
    Peng YD, Meng K, Guan HQ, Leng L, Zhu RR et al. 2020.. [ Clinical characteristics and outcomes of 112 cardiovascular disease patients infected by 2019-nCoV. ]. Zhonghua Xin Xue Guan Bing Za Zhi [Chin. J. Cardiol.] 486450–55 (in Chinese)
    [Google Scholar]
  94. 94.
    Phung DT, Wang Z, Rutherford S, Huang C, Chu C. 2013. Body mass index and risk of pneumonia: a systematic review and meta-analysis. Obes. Rev. 14:839–57
     [Google Scholar]
  95. 95.
    Pulendran B, Maddur MS. 2015. Innate immune sensing and response to influenza. Curr. Top. Microbiol. Immunol. 386:23–71
     [Google Scholar]
  96. 96.
    Radigan KA, Morales-Nebreda L, Soberanes S, Nicholson T, Nigdelioglu R et al. 2014. Impaired clearance of influenza A virus in obese, leptin receptor deficient mice is independent of leptin signaling in the lung epithelium and macrophages. PLOS ONE 9:e108138
     [Google Scholar]
  97. 97.
    Ramon S, Baker SF, Sahler JM, Kim N, Feldsott EA et al. 2014. The specialized proresolving mediator 17-HDHA enhances the antibody-mediated immune response against influenza virus: A new class of adjuvant?. J. Immunol. 193:6031–40
     [Google Scholar]
  98. 98.
    Ramon S, Gao F, Serhan CN, Phipps RP. 2012. Specialized proresolving mediators enhance human B cell differentiation to antibody-secreting cells. J. Immunol. 189:1036–42
     [Google Scholar]
  99. 99.
    Rebeles J, Green WD, Alwarawrah Y, Nichols AG, Eisner W et al. 2019. Obesity-induced changes in T-cell metabolism are associated with impaired memory T-cell response to influenza and are not reversed with weight loss. J. Infect. Dis. 219:1652–61
     [Google Scholar]
  100. 100.
    Rena G, Hardie DG, Pearson ER. 2017. The mechanisms of action of metformin. Diabetologia 60:1577–85
     [Google Scholar]
  101. 101.
    Sahanic S, Loffler-Ragg J, Tymoszuk P, Hilbe R, Demetz E et al. 2021. The role of innate immunity and bioactive lipid mediators in COVID-19 and influenza. Front. Physiol. 12:688946
     [Google Scholar]
  102. 102.
    Saltiel AR, Olefsky JM. 2017. Inflammatory mechanisms linking obesity and metabolic disease. J. Clin. Investig. 127:1–4
     [Google Scholar]
  103. 103.
    Saucillo DC, Gerriets VA, Sheng J, Rathmell JC, Maciver NJ. 2014. Leptin metabolically licenses T cells for activation to link nutrition and immunity. J. Immunol. 192:136–44
     [Google Scholar]
  104. 104.
    Saunders-Hastings PR, Krewski D 2016. Reviewing the history of pandemic influenza: understanding patterns of emergence and transmission. Pathogens 5:466
     [Google Scholar]
  105. 105.
    Serhan CN. 2014. Pro-resolving lipid mediators are leads for resolution physiology. Nature 510:92–101
     [Google Scholar]
  106. 106.
    Serhan CN, Levy BD. 2018. Resolvins in inflammation: emergence of the pro-resolving superfamily of mediators. J. Clin. Investig. 128:2657–69
     [Google Scholar]
  107. 107.
    Shi LZ, Wang R, Huang G, Vogel P, Neale G et al. 2011. HIF1α-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells. J. Exp. Med. 208:1367–76
     [Google Scholar]
  108. 108.
    Siegel ER, Croze RH, Fang X, Matthay MA, Gotts JE. 2021. Inhibition of the lipoxin A4 and resolvin D1 receptor impairs host response to acute lung injury caused by pneumococcal pneumonia in mice. Am. J. Physiol. Lung Cell. Mol. Physiol. 320:L1085–92
     [Google Scholar]
  109. 109.
    Simonnet A, Chetboun M, Poissy J, Raverdy V, Noulette J et al. 2020. High prevalence of obesity in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) requiring invasive mechanical ventilation. Obesity 28:1195–99
     [Google Scholar]
  110. 110.
    Simopoulos AP, Serhan CN, Bazinet RP. 2021. The need for precision nutrition, genetic variation and resolution in Covid-19 patients. Mol. Aspects Med. 77:100943
     [Google Scholar]
  111. 111.
    Skountzou I, Koutsonanos DG, Kim JH, Powers R, Satyabhama L et al. 2010. Immunity to pre-1950 H1N1 influenza viruses confers cross-protection against the pandemic swine-origin 2009 A (H1N1) influenza virus. J. Immunol. 185:1642–49
     [Google Scholar]
  112. 112.
    Smith AG, Sheridan PA, Harp JB, Beck MA. 2007. Diet-induced obese mice have increased mortality and altered immune responses when infected with influenza virus. J. Nutr. 137:1236–43
     [Google Scholar]
  113. 113.
    Smith AG, Sheridan PA, Tseng RJ, Sheridan JF, Beck MA. 2009. Selective impairment in dendritic cell function and altered antigen-specific CD8+ T-cell responses in diet-induced obese mice infected with influenza virus. Immunology 126:268–79
     [Google Scholar]
  114. 114.
    Soffer S, Glicksberg BS, Zimlichman E, Efros O, Levin MA et al. 2021. The association between obesity and peak antibody titer response in COVID-19 infection. Obesity 29:1547–53
     [Google Scholar]
  115. 115.
    Sun Q, Li J, Gao F. 2014. New insights into insulin: the anti-inflammatory effect and its clinical relevance. World J. Diabetes 5:89–96
     [Google Scholar]
  116. 116.
    Teague H, Fhaner CJ, Harris M, Duriancik DM, Reid GE, Shaikh SR. 2013. n-3 PUFAs enhance the frequency of murine B-cell subsets and restore the impairment of antibody production to a T-independent antigen in obesity. J. Lipid Res. 54:3130–38
     [Google Scholar]
  117. 117.
    Teague H, Harris M, Fenton J, Lallemand P, Shewchuk B, Shaikh SR. 2014. Eicosapentaenoic and docosahexaenoic acid ethyl esters differentially enhance B-cell activity in murine obesity. J. Lipid Res. 55:420–33
     [Google Scholar]
  118. 118.
    Titos E, Rius B, Lopez-Vicario C, Alcaraz-Quiles J, Garcia-Alonso V et al. 2016. Signaling and immunoresolving actions of resolvin D1 in inflamed human visceral adipose tissue. J. Immunol. 197:3360–70
     [Google Scholar]
  119. 119.
    Tsai S, Clemente-Casares X, Zhou AC, Lei H, Ahn JJ et al. 2018. Insulin receptor-mediated stimulation boosts T cell immunity during inflammation and infection. Cell Metab. 28:922–34.e4
     [Google Scholar]
  120. 120.
    Urra JM, Cabrera CM, Porras L, Rodenas I. 2020. Selective CD8 cell reduction by SARS-CoV-2 is associated with a worse prognosis and systemic inflammation in COVID-19 patients. Clin. Immunol. 217:108486
     [Google Scholar]
  121. 121.
    van der Windt GJ, Everts B, Chang CH, Curtis JD, Freitas TC et al. 2012. Mitochondrial respiratory capacity is a critical regulator of CD8+ T cell memory development. Immunity 36:68–78
     [Google Scholar]
  122. 122.
    van Niekerk G, Christowitz C, Conradie D, Engelbrecht AM. 2020. Insulin as an immunomodulatory hormone. Cytokine Growth Factor Rev. 52:34–44
     [Google Scholar]
  123. 123.
    Vander Heiden MG, Cantley LC, Thompson CB. 2009. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 324:1029–33
     [Google Scholar]
  124. 124.
    Watanabe M, Balena A, Tuccinardi D, Tozzi R, Risi R et al. 2021. Central obesity, smoking habit, and hypertension are associated with lower antibody titres in response to COVID-19 mRNA vaccine. Diabetes Metab. Res. Rev. 38:e3465
     [Google Scholar]
  125. 125.
    Winer D, Winer S, Shen L, Wadia P, Yantha J et al. 2011. B cells promote insulin resistance through modulation of T cells and production of pathogenic IgG antibodies. Nat. Med. 17:610–17
     [Google Scholar]
  126. 126.
    Winer S, Chan Y, Paltser G, Truong D, Tsui H et al. 2009. Normalization of obesity-associated insulin resistance through immunotherapy. Nat. Med. 15:921–29
     [Google Scholar]
  127. 127.
    Wu D, Molofsky AB, Liang H-E, Ricardo-Gonzalez RR, Jouihan HA et al. 2011. Eosinophils sustain adipose alternatively activated macrophages associated with glucose homeostasis. Science 332:243–47
     [Google Scholar]
  128. 128.
    Wu J, Li W, Shi X, Chen Z, Jiang B et al. 2020. Early antiviral treatment contributes to alleviate the severity and improve the prognosis of patients with novel coronavirus disease (COVID-19). J. Intern. Med. 288:128–38
     [Google Scholar]
  129. 129.
    Ye J. 2013. Mechanisms of insulin resistance in obesity. Front. Med. 7:14–24
     [Google Scholar]
  130. 130.
    Ying W, Lee YS, Dong Y, Seidman JS, Yang M et al. 2019. Expansion of islet-resident macrophages leads to inflammation affecting β cell proliferation and function in obesity. Cell Metab. 29:457–74.e5
     [Google Scholar]
  131. 131.
    Yu KK, Fischinger S, Smith MT, Atyeo C, Cizmeci D et al. 2021. Comorbid illnesses are associated with altered adaptive immune responses to SARS-CoV-2. JCI Insight 6:e146242
     [Google Scholar]
  132. 132.
    Yu Y, Liu Y, Shi FD, Zou H, Matarese G, La Cava A. 2013. Cutting edge: Leptin-induced RORγt expression in CD4+ T cells promotes Th17 responses in systemic lupus erythematosus. J. Immunol. 190:3054–58
     [Google Scholar]
  133. 133.
    Zhao X, Gang X, He G, Li Z, Lv Y et al. 2020. Obesity increases the severity and mortality of influenza and COVID-19: a systematic review and meta-analysis. Front. Endocrinol. 11:595109
     [Google Scholar]
  134. 134.
    Zheng C, Yang Q, Xu C, Shou P, Cao J et al. 2015. CD11b regulates obesity-induced insulin resistance via limiting alternative activation and proliferation of adipose tissue macrophages. PNAS 112:E7239–48
     [Google Scholar]
  135. 135.
    Zhou X, Zhu X, Li C, Li Y, Ye Z et al. 2021. Stearoyl-CoA desaturase-mediated monounsaturated fatty acid availability supports humoral immunity. Cell Rep 34:108601
     [Google Scholar]
/content/journals/10.1146/annurev-nutr-062320-115937
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Obesity Dysregulates the Immune Response to Influenza Infection and Vaccination Through Metabolic and Inflammatory Mechanisms
Annual Review of Nutrition 42, 67 (2022); https://doi.org/10.1146/annurev-nutr-062320-115937
/content/journals/10.1146/annurev-nutr-062320-115937
/content/journals/10.1146/annurev-nutr-062320-115937
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