Departamento de Sanidad Animal, Facultad de Veterinaria, Instituto de Ganadería de Montaña (CSIC-ULE), Universidad de León, C/ Profesor Pedro Cármenes s/n, E-24071, León, Spain.
BMC Vet Res. 2022 Aug 4;18(1):299. doi: 10.1186/s12917-022-03399-x.
Mycobacterium avium subsp. paratuberculosis infected animals show a variety of granulomatous lesions, from focal forms with well-demarcated granulomas restricted to the gut-associated lymphoid tissue (GALT), that are seen in the initial phases or latency stages, to a diffuse granulomatous enteritis, with abundant (multibacillary) or scant (paucibacillary) bacteria, seen in clinical stages. Factors that determine the response to the infection, responsible for the occurrence of the different types of lesion, are still not fully determined. It has been seen that regulatory T cells (Treg) play an important role in various diseases where they act on the limitation of the immunopathology associated with the immune response. In the case of paratuberculosis (PTB) the role of Treg lymphocytes in the immunity against Map is far away to be completely understood; therefore, several studies addressing this subject have appeared recently. The aim of this work was to assess, by immunohistochemical methods, the presence of Foxp3 T lymphocytes in intestinal samples with different types of lesions seen in cows with PTB.
Intestinal samples of twenty cows showing the different pathological forms of PTB were evaluated: uninfected controls (n = 5), focal lesions (n = 5), diffuse paucibacillary (n = 5) and diffuse multibacillary (n = 5) forms. Foxp3 lymphocyte distribution was assessed by differential cell count in intestinal lamina propria (LP), gut-associated lymphoid tissue (GALT) and mesenteric lymph node (MLN).
A significant increase in the number of Foxp3 T cells was observed in infected animals with respect to control group, regardless of the type of lesion. However, when the different categories of lesion were analyzed independently, all individuals with PTB lesions showed an increase in the amount of Foxp3 T lymphocytes compared to the control group but this increase was only significant in cows with focal lesions and, to a lesser extent, in animals with diffuse paucibacillary forms. The former showed the highest numbers, significantly different from those found in cows with diffuse lesions, where no differences were noted between the two forms. No specific distribution pattern was observed within the granulomatous lesions in any of the groups.
The increase of Foxp3 T cells in focal forms, that have been associated with latency or resistance to infection, suggest an anti-inflammatory action of these cells at these stages, helping to prevent exacerbation of the inflammatory response, as occurs in diffuse forms, responsible for the appearance of clinical signs.
感染分枝杆菌副结核亚种的动物表现出各种肉芽肿病变，从局限于肠相关淋巴组织（GALT）的具有明确界限的肉芽肿的局灶性形式，到临床阶段中大量（多菌型）或少量（少菌型）细菌的弥漫性肉芽肿性肠炎，在潜伏期或潜伏阶段都可见到。决定对感染的反应的因素，导致不同类型病变的发生，仍未完全确定。已经看到调节性 T 细胞（Treg）在各种疾病中发挥重要作用，它们作用于与免疫反应相关的免疫病理学的限制。在副结核病（PTB）的情况下，Treg 淋巴细胞在针对 Map 的免疫中的作用远未完全理解；因此，最近出现了几项针对该主题的研究。本研究的目的是通过免疫组织化学方法评估在患有 PTB 的牛的不同类型病变的肠组织样本中 Foxp3 T 淋巴细胞的存在。
评估了 20 头具有不同 PTB 病理形式的牛的肠组织样本：未感染对照（n=5）、局灶性病变（n=5）、弥漫性少菌型（n=5）和弥漫性多菌型（n=5）。通过肠固有层（LP）、肠相关淋巴组织（GALT）和肠系膜淋巴结（MLN）的差异细胞计数评估 Foxp3 淋巴细胞的分布。
与对照组相比，感染动物的 Foxp3 T 细胞数量显著增加，无论病变类型如何。然而，当独立分析不同类别的病变时，所有患有 PTB 病变的动物的 Foxp3 T 淋巴细胞数量均增加，但仅在局灶性病变的牛中以及在程度较轻的弥漫性少菌型动物中观察到这种增加具有统计学意义。前者显示的数量最高，与对照组有显著差异，而弥漫性病变的两组之间没有差异。在任何一组的肉芽肿病变中均未观察到特定的分布模式。
在与潜伏或感染抵抗相关的局灶性形式中 Foxp3 T 细胞的增加表明这些细胞在这些阶段具有抗炎作用，有助于防止炎症反应的加剧，如在弥漫性形式中发生的那样，这是临床症状出现的原因。
