Fimlaid Kelly A, Lindow Janet C, Tribble David R, Bunn Janice Y, Maue Alexander C, Kirkpatrick Beth D
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.
University of Vermont College of Medicine, Vaccine Testing Center and Unit of Infectious Diseases, Burlington, Vermont, United States of America.
PLoS One. 2014 Nov 14;9(11):e112513. doi: 10.1371/journal.pone.0112513. eCollection 2014.
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.
空肠弯曲菌是全球人类肠胃炎的主要病因；然而，我们对人类针对空肠弯曲菌感染的免疫反应的了解有限。先前的人类挑战模型表明，空肠弯曲菌可诱导外周血单核细胞产生γ干扰素，这种反应与再次感染后预防临床疾病有关。在本研究中，我们使用一种新的人类挑战模型的标本，调查与弯曲菌病相关的T淋巴细胞谱，在该模型中，未接触过空肠弯曲菌的受试者接受空肠弯曲菌CG8421的初次和再次挑战。多参数流式细胞术用于研究作为细胞因子（包括γ干扰素）来源的T淋巴细胞，并识别与弯曲菌病或预防疾病相关的细胞因子模式。出乎意料的是，除一名受试者外，所有接受评估的受试者在再次挑战后都再次出现了弯曲菌病。我们发现，CD4+T细胞在感染后会产生γ干扰素和其他促炎细胞因子；然而，未发现多功能细胞因子反应模式。再次挑战后，外周CD4+T细胞的细胞因子产生并未增强，这可能表明细胞发生了缺失或耐受。需要评估其他范例或模型，以更好地了解预防弯曲菌病的免疫成分。
