San Mateo L R, Toffer K L, Orndorff P E, Kawula T H
Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA.
Infect Immun. 1999 Sep;67(9):4963-7. doi: 10.1128/IAI.67.9.4963-4967.1999.
Cutaneous lesions of the human sexually transmitted genital ulcer disease chancroid are characterized by the presence of intraepidermal pustules, keratinocyte cytopathology, and epidermal and dermal erosion. These lesions are replete with neutrophils, macrophages, and CD4(+) T cells and contain very low numbers of cells of Haemophilus ducreyi, the bacterial agent of chancroid. We examined lesion formation by H. ducreyi in a pig model by using cyclophosphamide (CPA)-induced immune cell deficiency to distinguish between host and bacterial contributions to chancroid ulcer formation. Histologic presentation of H. ducreyi-induced lesions in CPA-treated pigs differed from ulcers that developed in immune-competent animals in that pustules did not form and surface epithelia remained intact. However, these lesions had significant suprabasal keratinocyte cytotoxicity. These results demonstrate that the host immune response was required for chancroid ulceration, while bacterial products were at least partially responsible for the keratinocyte cytopathology associated with chancroid lesions in the pig. The low numbers of H. ducreyi present in lesions in humans and immune-competent pigs have prevented localization of these organisms within skin. However, H. ducreyi organisms were readily visualized in lesion biopsies from infected CPA-treated pigs by immunoelectron microscopy. These bacteria were extracellular and associated with necrotic host cells in the epidermis and dermis. The relative abundance of H. ducreyi in inoculated CPA-treated pig skin suggests control of bacterial replication by host immune cells during natural human infection.
人类性传播的生殖器溃疡疾病软下疳的皮肤病变特征为表皮内脓疱、角质形成细胞细胞病理学改变以及表皮和真皮糜烂。这些病变富含中性粒细胞、巨噬细胞和CD4(+) T细胞，且含有极少量的杜克雷嗜血杆菌（软下疳的病原体）。我们通过使用环磷酰胺（CPA）诱导的免疫细胞缺陷，在猪模型中研究了杜克雷嗜血杆菌引起的病变形成，以区分宿主和细菌对软下疳溃疡形成的作用。CPA处理的猪中杜克雷嗜血杆菌诱导的病变的组织学表现与免疫健全动物中形成的溃疡不同，即不形成脓疱且表面上皮保持完整。然而，这些病变具有显著的基底上层角质形成细胞细胞毒性。这些结果表明，宿主免疫反应是软下疳溃疡形成所必需的，而细菌产物至少部分导致了与猪软下疳病变相关的角质形成细胞细胞病理学改变。人类和免疫健全猪病变中存在的少量杜克雷嗜血杆菌阻碍了这些微生物在皮肤内的定位。然而，通过免疫电子显微镜在感染CPA处理猪的病变活检中很容易观察到杜克雷嗜血杆菌。这些细菌位于细胞外，与表皮和真皮中的坏死宿主细胞相关。接种CPA处理猪皮肤中杜克雷嗜血杆菌的相对丰度表明，在自然人类感染期间，宿主免疫细胞对细菌复制有控制作用。
