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在绵羊潜伏和活跃的衣原体感染期间定义免疫相关性。

Defining immune correlates during latent and active chlamydial infection in sheep.

机构信息

Moredun Research Institute, International Research Centre, Pentlands Science Park, Bush Loan, Penicuik, Scotland, EH26 0PZ, UK.

School of Applied Sciences, Napier University, Edinburgh, Scotland, EH11 4BN, UK.

出版信息

Vet Res. 2020 Jun 1;51(1):75. doi: 10.1186/s13567-020-00798-6.

DOI:10.1186/s13567-020-00798-6
PMID:32487248
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7268686/
Abstract

Ovine enzootic abortion (OEA) caused by the obligate intracellular bacterial pathogen Chlamydia abortus (C. abortus), is an endemic disease in most sheep-rearing countries worldwide. Following infection, C. abortus establishes a complex host-pathogen interaction with a latent phase in non-pregnant sheep followed by an active disease phase in the placenta during pregnancy leading to OEA. Improved knowledge of the host-pathogen interactions at these different phases of disease will accelerate the development of new diagnostic tests and vaccines to control OEA. Current evidence indicates that cellular immunity is essential for controlling C. abortus infection. We have previously described a model of mucosal (intranasal) infection of non-pregnant sheep with C. abortus that replicates the latent and active phases of OEA. We have investigated antigen-specific recall responses of peripheral blood mononuclear cells (PBMC) in sheep infected with C. abortus via the intranasal route to determine how these change during the latent and active phases of disease. By analysing cytokines associated with the major CD4 T (T) cell subsets (Interferon-gamma (IFN-γ)/T1; Interleukin (IL)-4/T2; IL-17A/T17; IL-10/T), we show that there is selective activation of PBMC producing IFN-γ and/or IL-10 during the latent phase following infection. These cytokines are also elevated during the active disease phase and while they are produced by sheep that are protected from OEA, they are also produced by sheep that abort, highlighting the difficulties in finding specific cellular immunological correlates of protection for complex intracellular pathogens.

摘要

绵羊地方性流产（Ovine enzootic abortion，OEA）由专性细胞内细菌病原体沙眼衣原体（Chlamydia abortus，C. abortus）引起，是世界上大多数养羊国家的地方性疾病。感染后，C. abortus 在非怀孕绵羊中建立了一个复杂的宿主-病原体相互作用，在怀孕期间的胎盘中有一个潜伏阶段，随后是一个活跃的疾病阶段，导致 OEA。对这些不同疾病阶段的宿主-病原体相互作用的更好理解将加速新的诊断测试和疫苗的开发，以控制 OEA。目前的证据表明，细胞免疫对于控制 C. abortus 感染至关重要。我们之前描述了一种非怀孕绵羊鼻腔（鼻内）感染 C. abortus 的模型，该模型复制了 OEA 的潜伏和活跃阶段。我们研究了通过鼻腔途径感染 C. abortus 的绵羊外周血单核细胞（peripheral blood mononuclear cells，PBMC）的抗原特异性回忆反应，以确定这些反应在疾病的潜伏和活跃阶段如何变化。通过分析与主要 CD4 T（T）细胞亚群（干扰素-γ（IFN-γ）/T1；白细胞介素（IL）-4/T2；IL-17A/T17；IL-10/T）相关的细胞因子，我们表明在感染后的潜伏阶段，产生 IFN-γ 和/或 IL-10 的 PBMC 选择性激活。这些细胞因子在活跃的疾病阶段也会升高，虽然它们是由免受 OEA 保护的绵羊产生的，但它们也由流产的绵羊产生，这突出了为复杂的细胞内病原体找到特定的细胞免疫保护相关性的困难。

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