Chronic intestinal inflammation typically associated with late stage Johne's disease (JD) in cattle occurs despite a lack of significant expression of the typical proinflammatory cytokines IFNγ and TNFα derived from Th1- like T cells. In contrast, these cytokines appear to be relatively abundant during early infections with Mycobacterium avium subspecies paratuberculosis (MAP), the causative agent of JD in cattle. The roles of non-classical immune responses, such as those associated with Th17 cells, in response to MAP infection and development of clinical JD are less clear. In this review, we examine literature suggesting that Mycobacterial infections, including Mycobacterium tuberculosis, Mycobacterium bovis, and MAP, are all associated with expression of Th17 promoting cytokines (IL-23, IL-22, IL-17a). We discuss the possibility that Th17 associated cytokines, particularly IL-23, may act as contributing factors in development and maintenance of inflammation characteristic of clinical JD. An as yet relatively unexplored source of chronic inflammation due to over expression of IL-1α and IL-1β is also presented. We further discuss the fact that, as with the typical Th1-like cytokines IFNγ and TNFα , IL-17a is not significantly expressed in CD4+ T cells from cows with clinical JD, possibly due to T cell exhaustion. Finally, we present the notion that the Th17 driving cytokine IL-23 expressed by infected macrophages and associated epithelial cells may contribute to chronic inflammation during later stages of JD.

中文翻译：

---

牛体内结核分枝杆菌亚种（MAP）感染后的炎性Th17反应及其在约翰氏病发展中的潜在作用。

尽管缺乏从Th1样T细胞衍生的典型促炎细胞因子IFNγ和TNFα的显着表达，但通常发生与牛的晚期约翰尼氏病（JD）相关的慢性肠道炎症。相反，在牛分枝杆菌亚种副结核病（MAP）（牛中JD的病原体）的早期感染期间，这些细胞因子似乎相对丰富。非经典免疫反应（如与Th17细胞相关的免疫反应）对MAP感染和临床JD发展的作用尚不清楚。在这篇综述中，我们检查了暗示结核分枝杆菌，牛分枝杆菌和MAP在内的分枝杆菌感染均与Th17促进细胞因子（IL-23，IL-22，IL-17a）的表达有关。我们讨论了与Th17相关的细胞因子，尤其是IL-23，可能充当发展和维持临床JD炎症特征的因素的可能性。还提出了由于IL-1α和IL-1β的过表达而引起的慢性炎症的相对尚未探索的来源。我们进一步讨论以下事实：与典型的Th1类细胞因子IFNγ和TNFα一样，IL-17a在患有临床JD的母牛的CD4 + T细胞中未显着表达，可能是由于T细胞衰竭所致。最后，我们提出了这样的观念，即感染巨噬细胞和相关上皮细胞表达的Th17驱动细胞因子IL-23可能在JD后期阶段导致慢性炎症。可能是发展和维持临床JD炎症特征的促成因素。还提出了由于IL-1α和IL-1β的过表达而引起的慢性炎症的相对尚未探索的来源。我们进一步讨论以下事实：与典型的Th1类细胞因子IFNγ和TNFα一样，IL-17a在患有临床JD的母牛的CD4 + T细胞中未显着表达，可能是由于T细胞衰竭所致。最后，我们提出了这样的观念，即感染巨噬细胞和相关上皮细胞表达的Th17驱动细胞因子IL-23可能在JD后期阶段导致慢性炎症。可能是发展和维持临床JD炎症特征的促成因素。还提出了由于IL-1α和IL-1β的过表达而引起的慢性炎症的相对尚未探索的来源。我们进一步讨论以下事实：与典型的Th1类细胞因子IFNγ和TNFα一样，IL-17a在患有临床JD的母牛的CD4 + T细胞中未显着表达，可能是由于T细胞衰竭所致。最后，我们提出了这样一种观念，即感染巨噬细胞和相关上皮细胞表达的Th17驱动细胞因子IL-23可能在JD后期阶段导致慢性炎症。IL-17a在患有临床JD的母牛的CD4 + T细胞中没有明显表达，可能是由于T细胞衰竭所致。最后，我们提出了这样一种观念，即感染巨噬细胞和相关上皮细胞表达的Th17驱动细胞因子IL-23可能在JD后期阶段导致慢性炎症。IL-17a在患有临床JD的母牛的CD4 + T细胞中没有明显表达，可能是由于T细胞衰竭所致。最后，我们提出了这样的观念，即感染巨噬细胞和相关上皮细胞表达的Th17驱动细胞因子IL-23可能在JD后期阶段导致慢性炎症。