Chronic Alcohol Ingestion Delays T Cell Activation and Effector Function in Sepsis

• Published in: PloS one Vol. 11; no. 11; p. e0165886
• Main Authors: Margoles, Lindsay M, Mittal, Rohit, Klingensmith, Nathan J, Lyons, John D, Liang, Zhe, Serbanescu, Mara A, Wagener, Maylene E, Coopersmith, Craig M, Ford, Mandy L
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 18-11-2016; Public Library of Science (PLoS)
• Subjects: Alcohol use; Alcoholic beverages; Alcohols - administration & dosage; Animal models; Animals; Antigens; Apoptosis; Biology and Life Sciences; Biomarkers; CD4 antigen; CD43 antigen; CD44 antigen; CD69 antigen; CD8 antigen; Cecum; Cell activation; Cell growth; Cellular biology; Cytokines; Cytokines - metabolism; Cytotoxicity; Disease Models, Animal; Disease susceptibility; Drinking (Alcoholic beverages); Ethanol; Flow Cytometry; Glycosylation - drug effects; Health aspects; Hepatitis; Hospitals; Hypersensitivity; Hypersensitivity (delayed); Immune response; Immune system; Immunity; Immunologic Memory - drug effects; Immunology; Infection; Infections; Ingestion; Innate immunity; Intensive care units; Interleukin 2; Lymphocyte Activation - drug effects; Lymphocyte Activation - immunology; Lymphocyte Count; Lymphocytes; Lymphocytes T; Male; Medicine and Health Sciences; Mice; Mortality; Physical Sciences; Pneumonia; Qualitative analysis; Response time; Sepsis; Sepsis - immunology; Sepsis - metabolism; Surgery; T cell receptors; T cells; T-Lymphocyte Subsets - drug effects; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; Time Factors; Trends; Tumor necrosis factor; γ-Interferon; Atlanta Georgia; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0165886

Sepsis is the leading cause of death in intensive care units in the US, and it is known that chronic alcohol use is associated with higher incidence of sepsis, longer ICU stays, and higher mortality from sepsis. Both sepsis and chronic alcohol use are associated with immune deficits such as decreased lymphocyte numbers, impaired innate immunity, delayed-type hypersensitivity reactions, and susceptibility to infections; however, understanding of specific pathways of interaction or synergy between these two states of immune dysregulation is lacking. This study therefore sought to elucidate mechanisms underlying the immune dysregulation observed during sepsis in the setting of chronic alcohol exposure. Using a murine model of chronic ethanol ingestion followed by sepsis induction via cecal ligation and puncture, we determined that while CD4+ and CD8+ T cells isolated from alcohol fed mice eventually expressed the same cellular activation markers (CD44, CD69, and CD43) and effector molecules (IFN-γ, TNF) as their water fed counterparts, there was an overall delay in the acquisition of these phenotypes. This early lag in T cell activation was associated with significantly reduced IL-2 production at a later timepoint in both the CD4+ and CD8+ T cell compartments in alcohol sepsis, as well as with a reduced accumulation of CD8dim activated effectors. Taken together, these data suggest that delayed T cell activation may result in qualitative differences in the immune response to sepsis in the setting of chronic alcohol ingestion.