Alexander Kathleen A, Laver Peter N, Williams Mark C, Sanderson Claire E, Kanipe Carly, Palmer Mitchell V
1 Department of Fish and Wildlife Conservation, Virginia Tech, Blacksburg, VA, USA.
2 CARACAL, Centre for Conservation of African Resources, Animals, Communities, and Land Use, Kasane, Botswana.
Vet Pathol. 2018 Mar;55(2):303-309. doi: 10.1177/0300985817741730. Epub 2017 Dec 19.
Wild banded mongooses ( Mungos mungo) in northeastern Botswana and northwest Zimbabwe are infected with a novel Mycobacterium tuberculosis complex (MTC) pathogen, Mycobacterium mungi. We evaluated gross and histologic lesions in 62 infected mongooses (1999-2017). Many tissues contained multifocal irregular, lymphohistiocytic to granulomatous infiltrates and/or multifocal or coalescing noncaseating to caseating granulomas with variable numbers of intralesional acid-fast bacilli. Over one-third of nasal turbinates examined had submucosal lymphohistiocytic to granulomatous infiltrates, erosion and ulceration of the nasal mucosa, bony remodeling, and nasal distortion. Similar inflammatory cell infiltrates expanded the dermis of the nasal planum with frequent ulceration. However, even in cases with intact epidermis, acid-fast bacilli were present in variable numbers among dermal infiltrates and on the epidermal surface among desquamated cells and debris, most commonly in small crevices or folds. In general, tissue involvement varied among cases but was highest in lymph nodes (50/54, 93%), liver (39/53, 74%), spleen (37/51, 73%), and anal glands/sacs (6/8, 75%). Pulmonary lesions were present in 67% of sampled mongooses (35/52) but only in advanced disseminated disease. The pathological presentation of M. mungi in the banded mongoose is consistent with pathogen shedding occurring through scent-marking behaviors (urine and anal gland secretions) with new infections arising from contact with these contaminated olfactory secretions and percutaneous movement of the pathogen through breaks in the skin, nasal planum, and/or skin of the snout. Given the character and distribution of lesions and the presence of intracellular acid-fast bacilli, we hypothesize that pathogen spread occurs within the body through a hematogenous and/or lymphatic route. Features of prototypical granulomas such as multinucleated giant cells and peripheral fibrosis were rarely present in affected mongooses. Acid-fast bacilli were consistently found intracellularly, even in regions of necrosis. The mongoose genome has a unique deletion (RD1) that includes part of the encoding region for PPE68 (Rv3873), a gene co-operonic with PE35. These proteins can influence the host's cellular immune response to mycobacterial infections, and it remains uncertain how this deletion might contribute to observed patterns of pathology. M. mungi infection in banded mongooses is characterized by both a unique transmission and exposure route, as well as accompanying pathological features, providing an opportunity to increase our understanding of MTC pathogenesis across host-pathogen systems.
博茨瓦纳东北部和津巴布韦西北部的野生带状猫鼬（Mungos mungo）感染了一种新型结核分枝杆菌复合群（MTC）病原体——蒙氏分枝杆菌（Mycobacterium mungi）。我们评估了62只受感染猫鼬（1999 - 2017年）的大体和组织学病变。许多组织含有多灶性不规则的淋巴细胞 - 组织细胞性至肉芽肿性浸润和/或多灶性或融合性的非干酪样至干酪样肉芽肿，病灶内抗酸杆菌数量不等。超过三分之一接受检查的鼻甲骨有黏膜下淋巴细胞 - 组织细胞性至肉芽肿性浸润、鼻黏膜糜烂和溃疡、骨质重塑以及鼻变形。类似的炎性细胞浸润使鼻平面的真皮层增厚并频繁出现溃疡。然而，即使在表皮完整的病例中，抗酸杆菌也以不同数量存在于真皮浸润灶中以及脱屑细胞和碎屑中的表皮表面，最常见于小裂缝或褶皱处。一般来说，不同病例的组织受累情况各不相同，但在淋巴结（50/54，93%）、肝脏（39/53，74%）、脾脏（37/51，73%）和肛门腺/囊（6/8，75%）中最为常见。67%的采样猫鼬（35/52）存在肺部病变，但仅在晚期播散性疾病中出现。蒙氏分枝杆菌在带状猫鼬中的病理表现与通过气味标记行为（尿液和肛门腺分泌物）排出病原体一致，新的感染源于接触这些受污染的嗅觉分泌物以及病原体经皮肤、鼻平面和/或口鼻部皮肤破损处的经皮传播。鉴于病变的特征和分布以及细胞内抗酸杆菌的存在，我们推测病原体在体内通过血行和/或淋巴途径传播。受影响的猫鼬中很少出现典型肉芽肿的特征，如多核巨细胞和外周纤维化。即使在坏死区域，也始终能在细胞内发现抗酸杆菌。猫鼬基因组有一个独特的缺失（RD1），其中包括PPE68（Rv3873）编码区域的一部分，PPE68是一个与PE35共操纵子的基因。这些蛋白质可影响宿主对分枝杆菌感染的细胞免疫反应，目前尚不确定这种缺失如何导致观察到的病理模式。带状猫鼬中的蒙氏分枝杆菌感染具有独特的传播和暴露途径以及伴随的病理特征，为增进我们对跨宿主 - 病原体系统的MTC发病机制的理解提供了机会。
