Peripheral CD4+ T cell cytokine responses following human challenge and re-challenge with Campylobacter jejuni.
Campylobacter jejuni is a leading cause of human gastroenteritis worldwide; however, our understanding of the human immune response to C. jejuni infection is limited. A previous human challenge model has shown that C. jejuni elicits IFNγ production by peripheral blood mononuclear cells, a response associated with protection from clinical disease following re-infection. In this study, we investigate T lymphocyte profiles associated with campylobacteriosis using specimens from a new human challenge model in which C. jejuni-naïve subjects were challenged and re-challenged with C. jejuni CG8421. Multiparameter flow cytometry was used to investigate T lymphocytes as a source of cytokines, including IFNγ, and to identify cytokine patterns associated with either campylobacteriosis or protection from disease. Unexpectedly, all but one subject evaluated re-experienced campylobacteriosis after re-challenge. We show that CD4+ T cells make IFNγ and other pro-inflammatory cytokines in response to infection; however, multifunctional cytokine response patterns were not found. Cytokine production from peripheral CD4+ T cells was not enhanced following re-challenge, which may suggest deletion or tolerance. Evaluation of alternative paradigms or models is needed to better understand the immune components of protection from campylobacteriosis.
Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, Vermont, 05405, United States of America; University of Vermont College of Medicine, Vaccine Testing Center and Unit of Infectious Diseases, Burlington, Vermont, United States of America.
Kelly A
KA
Fimlaid
University of Vermont College of Medicine, Vaccine Testing Center and Unit of Infectious Diseases, Burlington, Vermont, United States of America.
Janet C
JC
Lindow
Infectious Disease Clinical Research Program, Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States of America.
David R
DR
Tribble
University of Vermont College of Mathematics, Burlington, Vermont, United States of America.
Janice Y
JY
Bunn
Naval Medical Research Center, Enteric Diseases Department, Silver Spring, Maryland, United States of America.
Alexander C
AC
Maue
Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, Vermont, 05405, United States of America; University of Vermont College of Medicine, Vaccine Testing Center and Unit of Infectious Diseases, Burlington, Vermont, United States of America.
Beth D
BD
Kirkpatrick
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002169:Campylobacter Infections / Q000276:immunology*; D016123:Campylobacter jejuni / Q000276:immunology*; D016207:Cytokines / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D018448:Models, Immunological; D012008:Recurrence
D016207:Cytokines