Diet-Induced Obese Mice Have Increased Mortality and Altered Immune Responses When Infected with Influenza Virus

Abstract

Obesity is associated with an impaired immune response, an increased susceptibility to bacterial infection, and a chronic increase in proinflammatory cytokines such as IL-6 and TNFalpha. However, few studies have examined the effect of obesity on the immune response to viral infections. Because infection with influenza is a leading cause of morbidity and mortality worldwide, we investigated the effect of obesity on early immune responses to influenza virus exposure. Diet-induced obese and lean control C57BL/6 mice were infected with influenza A/PR8/34, and lung pathology and immune responses were examined at d 0 (uninfected), 3, and 6, postinfection. Following infection, diet-induced obese mice had a significantly higher mortality rate than the lean controls and elevated lung pathology. Antiviral and proinflammatory cytokine mRNA production in the lungs of the infected mice was markedly different between obese and lean mice. IFNalpha and beta were only minimally expressed in the infected lungs of obese mice and there was a notable delay in expression of the proinflammatory cytokines IL-6 and TNFalpha. Additionally, obese mice had a substantial reduction in NK cell cytotoxicity. These data indicate that obesity inhibits the ability of the immune system to appropriately respond to influenza infection and suggests that obesity may lead to increased morbidity and mortality from viral infections.

Diet-Induced Obesity Impairs the T Cell Memory Response to Influenza Virus Infection

“…The high-fat diet (D12331) consisted of 16.4% protein, 25.5% carbohydrate (51% sucrose, 49% maltodextrin), and 58% fat (93% coconut oil, 7% soybean oil). Previous studies in our laboratory (19) and others (24,25) have confirmed that these diets result in significant DIO (increased body weight, increased body fat mass) in these mice. This induction of obesity had also been shown to be reversed in these animals by switching from high-to low-fat diet (25).…”

“…Lung viral titers were determined by a modified TCID 50 using hemagglutination as an endpoint, as previously described (19). Briefly, half of the right lobe of the lung was removed, weighed, and ground in 0.2 ml MEM.…”

“…We hypothesize this increased severity may be due to obesity decreasing memory cell-mediated defenses against heterosubtypic influenza infection. Previously, we demonstrated that influenza infected diet-induced obese (DIO) mice developed increased lung pathology, decreased expression of IFNa/b and delayed expression of proinflammatory cytokines and chemokines (19). In addition, dendritic cells (DCs) from obese mice failed to efficiently present influenza Ag to T cells (20).…”

Impact of obesity on mortality in hospitalized patients with pneumonia due to 2009 H1N1 Influenza A virus versus other etiologies.

“…[4][5][6][7] Animal studies indicate that the production of interferon is significantly decreased in diet-induced, obese mice when compared to lean, control animals. 15,16 Decreased production of interferon in obese patients may explain the poor outcomes associated with pneumonia due to 2009 H1N1 influenza A virus.…”

High Body Mass Has No Effect on Cellular and Innate Immunity in Siberian Hamsters (<i>Phodopus sungorus</i>)

“…It is also impaired in db/db mice and fa/fa rats whose mutation in leptin receptor gene [15,16]. Suppression of immune responses are also observed in diet-induced obese mice [17][18][19] or rats [20,21]. Both cellular and humoral immunity are dampened in overweight Mongolian gerbils (Meriones unguiculatus) [22].…”