Lack of Homologous Protection Against Campylobacter jejuni CG8421 in a Human Challenge Model
Lack of Homologous Protection Against Campylobacter jejuni CG8421 in a Human Challenge Model
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DOI：
10.1093/cid/cit454
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发表时间：
2013-10-15
影响因子：
11.8
通讯作者：
Tribble, David R.
中科院分区：
文献类型：
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作者：
Kirkpatrick, Beth D.;Lyon, Caroline E.;Tribble, David R.
背景空肠弯曲菌是腹泻的常见原因，并伴有严重的感染后后遗症。尽管有症状和无症状感染者都得到了确认，但保护性免疫力还没有得到很好的理解。以前的数据表明，干扰素γ（IFN-γ）可能与保护有关。为了更好地确定临床和免疫学发展的保护性免疫，以C。空肠，我们评估的能力，初步感染，以防止临床疾病后，第二次实验感染。受试者没有既往感染C.空肠接受C.空肠CG 8421，3个月后再激发。主要终点是弯曲杆菌病，定义为腹泻和/或全身体征。对住院患者进行密切监测。评价血清免疫球蛋白A（伊加）和免疫球蛋白G（IgG）、粪便伊加、伊加抗体分泌细胞（ASC）和IFN-γ产生。所有受试者均接受抗生素治疗，出院时临床表现良好。15名受试者发生了C.空肠CG 8421例，弯曲菌病14例（93.3%）。8例受试者接受了第二次攻毒，所有受试者均发生了严重程度相似的弯曲杆菌病。原发感染后的免疫应答包括血清伊加、IgG、ASC和IFN-γ产生。二次感染后的反应不太强烈。结论。在未经处理的健康成年人中，CG 8421的单次感染不能预防弯曲杆菌病。虽然保护已被证明与其他菌株和连续的环境暴露后，我们的工作强调了重要性，事先免疫，重复暴露，和菌株差异的保护性免疫C。空肠。
Background. Campylobacter jejuni is a common cause of diarrhea and is associated with serious postinfectious sequelae. Although symptomatic and asymptomatic infections are recognized, protective immunity is not well understood. Previous data suggests that interferon gamma (IFN-gamma) may be associated with protection. To better define the clinical and immunologic development of protective immunity to C. jejuni, we assessed the ability of an initial infection to prevent clinical illness after a second experimental infection.Methods. Subjects with no clinical or immunologic evidence of prior infection with C. jejuni received an initial challenge with C. jejuni CG8421 with rechallenge 3 months later. The primary endpoint was campylobacteriosis, as defined by diarrhea and/or systemic signs. Close inpatient monitoring was performed. Serum immunoglobulin A (IgA) and immunoglobulin G (IgG), fecal IgA, IgA antibody-secreting cells (ASCs), and IFN-gamma production were evaluated. All subjects were treated with antibiotics and were clinically well at discharge.Results. Fifteen subjects underwent a primary infection with C. jejuni CG8421; 14 (93.3%) experienced campylobacteriosis. Eight subjects received the second challenge, and all experienced campylobacteriosis with similar severity. Immune responses after primary infection included serum IgA, IgG, ASC, and IFN-gamma production. Responses were less robust after secondary infection.Conclusions. In naive healthy adults, a single infection with CG8421 did not protect against campylobacteriosis. Although protection has been demonstrated with other strains and after continuous environmental exposure, our work highlights the importance of prior immunity, repeated exposures, and strain differences in protective immunity to C. jejuni.