Vaccine & Infectious Disease Organization-International Vaccine Centre, University of Saskatchewan, Saskatoon, SK, Canada.
Department of Microbiology and Immunology, Centre for Microbial Diseases and Immunity Research, University of British Columbia, Vancouver, BC, Canada.
Front Immunol. 2020 May 29;11:1020. doi: 10.3389/fimmu.2020.01020. eCollection 2020.
Chronic enteric ssp. (MAP) infections are endemic in ruminants globally resulting in significant production losses. The mucosal immune responses occurring at the site of infection, specifically in Peyer's patches (PP), are not well-understood. The ruminant small intestine possesses two functionally distinct PPs. Discrete PPs function as mucosal immune induction sites and a single continuous PP, in the terminal small intestine, functions as a primary lymphoid tissue for B cell repertoire diversification. We investigated whether MAP infection of discrete vs. continuous PPs resulted in the induction of significantly different pathogen-specific immune responses and persistence of MAP infection. Surgically isolated intestinal segments in neonatal calves were used to target MAP infection to individual PPs. At 12 months post-infection, MAP persisted in continuous PP ( = 4), but was significantly reduced ( = 0.046) in discrete PP ( = 5). RNA-seq analysis revealed control of MAP infection in discrete PP was associated with extensive transcriptomic changes (1,707 differentially expressed genes) but MAP persistent in continuous PP elicited few host responses (4 differentially expressed genes). Cytokine gene expression in tissue and MAP-specific recall responses by mucosal immune cells isolated from PP, lamina propria and mesenteric lymph node revealed interleukin ( and as unique correlates of protection associated with decreased MAP infection in discrete PP. This study provides the first description of mucosal immune responses occurring in bovine discrete jejunal PPs and reveals that a significant reduction in MAP infection is associated with specific cytokine responses. Conversely, MAP infection persists in the continuous ileal PP with minimal perturbation of host immune responses. These data reveal a marked dichotomy in host-MAP interactions within the two functionally distinct PPs of the small intestine and identifies mucosal immune responses associated with the control of a mycobacterial infection in the natural host.
慢性肠型（MAP）感染在全球反刍动物中流行，导致严重的生产损失。感染部位（特别是派尔集合淋巴结（PP））发生的黏膜免疫反应尚未得到很好的理解。反刍动物小肠具有两个功能不同的 PP。离散的 PP 作为黏膜免疫诱导部位发挥作用，而在终末小肠中的单个连续 PP 则作为 B 细胞库多样化的主要淋巴组织发挥作用。我们研究了 MAP 感染离散型与连续型 PP 是否会导致明显不同的病原体特异性免疫反应和 MAP 感染的持续存在。在新生牛的手术分离肠段中，用于针对 MAP 感染的单个 PP。在感染后 12 个月，连续 PP 中 MAP 持续存在（=4），但离散 PP 中 MAP 显著减少（=0.046）（=5）。RNA-seq 分析表明，离散 PP 中 MAP 感染的控制与广泛的转录组变化（1707 个差异表达基因）相关，但在连续 PP 中持续存在的 MAP 引发的宿主反应很少（4 个差异表达基因）。从 PP、固有层和肠系膜淋巴结分离的黏膜免疫细胞的组织细胞因子基因表达和 MAP 特异性回忆反应表明，白细胞介素（和）是与离散 PP 中 MAP 感染减少相关的独特保护相关基因。本研究首次描述了牛离散空肠 PP 中发生的黏膜免疫反应，并揭示了 MAP 感染的显著减少与特定细胞因子反应相关。相反，MAP 感染在连续回肠 PP 中持续存在，宿主免疫反应几乎没有受到干扰。这些数据揭示了在小肠两个功能不同的 PP 中宿主-MAP 相互作用的明显二分法，并确定了与天然宿主中控制分枝杆菌感染相关的黏膜免疫反应。
