title: Chronic Alcohol Ingestion Delays T Cell Activation and Effector Function in Sepsis.
abstract: 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.
authors.affiliation: Division of Infectious Diseases, Emory University, Atlanta, GA, United States of America.
authors.forename: Lindsay M
authors.initials: LM
authors.lastname: Margoles
authors.affiliation: Department of Surgery, Emory University, Atlanta, GA, United States of America.
authors.forename: Rohit
authors.initials: R
authors.lastname: Mittal
authors.affiliation: Department of Surgery, Emory University, Atlanta, GA, United States of America.
authors.forename: Nathan J
authors.initials: NJ
authors.lastname: Klingensmith
authors.affiliation: Department of Surgery, Emory University, Atlanta, GA, United States of America.
authors.forename: John D
authors.initials: JD
authors.lastname: Lyons
authors.affiliation: Department of Surgery, Emory University, Atlanta, GA, United States of America.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Liang
authors.affiliation: Department of Surgery, Emory University, Atlanta, GA, United States of America.
authors.forename: Mara A
authors.initials: MA
authors.lastname: Serbanescu
authors.affiliation: Department of Surgery, Emory University, Atlanta, GA, United States of America.|Emory Transplant Center, Emory University, Atlanta, GA, United States of America.
authors.forename: Maylene E
authors.initials: ME
authors.lastname: Wagener
authors.affiliation: Department of Surgery, Emory University, Atlanta, GA, United States of America.|Emory Critical Care Center, Emory University, Atlanta, GA, United States of America.
authors.forename: Craig M
authors.initials: CM
authors.lastname: Coopersmith
authors.affiliation: Department of Surgery, Emory University, Atlanta, GA, United States of America.|Emory Transplant Center, Emory University, Atlanta, GA, United States of America.
authors.forename: Mandy L
authors.initials: ML
authors.lastname: Ford
mesh_terms: D000438:Alcohols / Q000008:administration & dosage*; D000818:Animals; D015415:Biomarkers; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006031:Glycosylation / Q000187:drug effects; D007156:Immunologic Memory / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology*; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D018805:Sepsis / Q000276:immunology* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors
chemical_list: D000438:Alcohols; D015415:Biomarkers; D016207:Cytokines