Induced T cell Dysfunction during Influenza Infections
Wednesday, September 03, 2014
|Emily Hemann, PhD and Kevin Legge, PhD
It is well known that chronic alcohol consumption compromises the human immune system. This fact is underscored when examining the susceptibility of chronic alcoholics to infectious disease. Alcoholic patients have greatly increased risks of infection with extracellular bacteria, intracellular bacteria, and viruses. Numerous reports have documented that alcoholics exhibit higher rates of bacterial pneumonia, sepsis, meningitis, and peritonitis. Among the best-studied examples of this increased predilection to severe respiratory disease following chronic alcohol abuse are bacterial pneumonias. In fact, Benjamin Rush, the Surgeon General of the Continental Army and a signer of the Declaration of Independence, as early as 1785 described alcoholics as susceptible to yellow fever, tuberculosis, and pneumonia. More recent studies have demonstrated that there is a two- to seven-fold greater incidence in mortality as well as increased morbidity in chronic alcohol-consuming individuals compared to non-alcoholic pneumonia patients.
Immunity and long term protection against influenza virus infections is conferred by two components of the adaptive immune response, namely, antibodies which neutralize the virus preventing infections, and T cells, which find and kill infected cells, thus limiting spreading of the virus to other cells and halting the infection. Prior work in Dr. Legge’s laboratory showed that chronic levels of alcohol predispose for an increased severity of disease – both symptoms and lethality – following influenza virus infection. In fact, chronic alcohol changed in a dramatic way what is typically a subclinical infection into a lethal outcome. This change in disease severity is in part due to alcohol’s effects on CD8 T cells. Chronic drinking can decrease the number of the CD8 T cells available to defend against the infection, as well as limit the ability of the remaining CD8 T cells to use one of their anti-viral tools. In this manner, chronic alcohol attacks the CD8 T cell immune response on two separate levels: limiting the number of cells that can fight the infection, and limiting the ability of the remaining cells to fight.
T cells utilize multiple tools – called effector functions – to limit and control pathogens. While their prior studies demonstrated the loss in CD8 T cell numbers and ability of the remaining CD8 T cells to make IFN gamma, it was unclear if and how many of the other tools CD8 T cells are known to utilize were effected by chronic alcohol. In their new manuscript Drs. Hemann, McGill and Legge show that that alcohol may have distinct effects on the effector ability of CD8 T cells, limiting or reducing some functions while leaving other effector functions intact. It is known that triggering of each specific effector pathway requires precise signals. Therefore, further mapping of which effector functions are altered, coupled with examination of pertinent molecules, could yield promising drug targets for reversal of the effects of alcohol on this important adaptive immune cell population.
The following on-line science news organizations have referred to the article published from Dr. Legge’s lab:
Medical Daily - Why Alcohol Abuse Is Associated With Bad Flu Bouts: Study Explains How Booze Impairs Your Immune System
Examiner.com - The flu hits drinkers harder as alcohol attacks T cells
Medical News Today – An abnormal CD8 T cell response to the influenza virus a problem for alcoholics
Health Medicine Network - Alcoholics have an abnormal CD8 T cell response to the influenza virus
ScienceDaily® - Alcoholics have an abnormal CD8 T cell response to the influenza virus
EurekAlert - Alcoholics have an abnormal CD8 T cell response to the influenza virus
MeD INDIA (Network For Health) - Abnormal CD8 T Cell Response to Influenza Virus Observed in Alcoholics
MedicalXpress - Alcoholics have an abnormal CD8 T cell response to the influenza virus
Science Newsline - Alcoholics Have an Abnormal CD8 T Cell Response to the Influenza Virus