New data identify weight-linked defects in the body’s immune responses
WASHINGTON, D.C. Think you’ll easily survive a bout of H1N1 swine flu? Fat chance – if you’re really fat. New research points to a likely explanation for this weighty vulnerability: a failure of the immune system to rev up as strongly as it should.
In 2009, obesity emerged for the first time as an independent risk factor for flu – but only for the H1N1 pandemic strain. To see whether immunity was behind this risk, Heather Paich of the University of North Carolina at Chapel Hill and her colleagues recruited participants for a new study from among local residents who had stopped off at a university clinic to get their flu shots.
Thirty days after those vaccinations, each participant came back to give blood. White blood cells – key players in fighting disease – were separated out and then challenged with a small dose of live H1N1 virus. Two important classes of these cells responded differently in the obese, Paich and her colleagues reported April 11 at the Experimental Biology meeting.
Dendritic cells present a virus to other immune cells, inviting them to attack it. CD8-positive T-cells are an important class of germ killers that receive the virus from those dendritic cells.
In blood from the lean people, H1N1 stimulation activated both types of cells, turning them into infection-fighting warriors. In blood from the obese recruits, the response proved much more anemic -- only about 70 percent as robust. Consistent with these changes, the H1N1-stimulated CD8-positive T-cells from obese participants also made 25 to 30 percent less of two important immune-signaling proteins: granzyme-B and interferon-gamma.
The elderly face a high susceptibly to flu and its complications. Many scientists believe that traces to a wimpy response by CD8 cells, says Patricia Sheridan, Paich’s teammate. Their new human immunity data now suggest that obesity may effectively lead to a premature senescence of integral parts of the immune system as is seen in the elderly.
Ordinarily, obese patients admitted to a hospital’s intensive care unit don’t have a higher rate of death than normal weight patients, observes Lena Napolitano, who heads trauma and surgical critical care at the University of Michigan Hospital in Ann Arbor. But H1N1 rewrote the rules, she says.
“We initially reported the first patients in the United States with severe acute respiratory distress syndrome, or ARDS, due to H1N1,” she says. In a report issued through the Centers for Disease Control and Prevention, Napolitano’s team described 10 of these patients encountered as the pandemic was building. On average only 49 years old, these patients “were on death’s door and had multiple organ failures.” All but one were obese – seven of them morbidly so.
Since then, other groups have confirmed obesity as a risk factor for H1N1 complications. Oliver Morgan and his colleagues at the CDC, for instance, reported in the March 15, 2010, PLoS One that being obese – especially morbidly obese – greatly increased an adult’s risk of dying during the initial 2009 wave of pandemic H1N1 infections. Even when his team restricted cases to adults without preexisting medical conditions that would normally be expected to put people at risk for flu complications, being obese tripled the risk of death; being morbidly obese increased the death rate to 7.6 times that seen in normal weight flu victims.
And it’s not just a historical problem, Napolitano points out. Her community is in the throes of a new wave of H1N1 cases, chiefly affecting unvaccinated adults. Among these, “We currently are still seeing a large number of patients with severe acute respiratory distress syndrome,” she says – most of whom are obese.
H. Paich, et al. Obese individuals demonstrate a defective response to influenza A virus infection compared with healthy weight individuals. Experimental Biology 2011 (American Society of Nutrition minisymposium, April 11.
E.A. Karlsson, P.A. Sheridan and M.A. Beck. Diet-induced obesity impairs the t cell memory response to influenza virus infection. Journal of Immunology, Vol. 184, March 15, 2010, p. 3127. doi:10.4049/jimmunol.0903220. [Go to]
C. Miller, et al. Intensive-care patients with severe novel influenza A (H1N1) virus infection — Michigan, June 2009. Morbidity and Mortality Weekly Report, Vol. 58, July 10, 2009, p. 1. [Go to]
O.W. Morgan, et al. Morbid obesity as a risk factor for hospitalization and death due to 2009 pandemic influenza A(H1N1) disease, PLoS One, Vol. 5, March 15, 2010, p. e9694. doi:10.1371/journal.pone.0009694. [Go to]
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