Laboratório Especial de Micologia, Disciplina de Infectologia, Departamento de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
Hospital do Rim, Fundação Oswaldo Ramos, Universidade Federal de São Paulo, SP, Brazil.
Pathog Dis. 2020 Oct 22;78(7). doi: 10.1093/femspd/ftaa054.
Cryptococcosis is the second most common invasive fungal infection reported in renal transplant recipients. Tissue granulomatous inflammation is necessary to contain Cryptococcus infection. This study aims to analyze the granuloma patterns and in situ expression of regulatory T (Treg) immune response in tissue samples from 12 renal transplant recipients with cryptococcosis. Fungal isolates were molecularly identified as Cryptococcus neoformans species complex. A detailed characterization of granulomas in tissue samples from 12 kidney transplant recipients with cryptococcosis was described by checking six lung and six skin biopsies by conventional histology and for immunohistochemical detection of CD4 and Treg markers: forkhead box P3 (FoxP3), interleukin (IL)-10 and transforming-growth factor (TGF)-β. Granulomas were classified as compact, loose or mixed. Patients with mixed (n = 4) and compact (n = 3) granulomatous inflammation patterns were associated with a better prognosis and presented a higher number of CD4+FoxP3+T cells compared to the group of patients with loose granulomas. In counterpart, three out of five patients with loose granulomas died with cryptococcosis. We suggest that Treg may have a protective role in the tissue response to Cryptococcus infection given its association with compact and mixed granulomas in patients with better clinical outcomes.
隐球菌病是肾移植受者中报告的第二大常见侵袭性真菌感染。组织肉芽肿性炎症对于控制隐球菌感染是必要的。本研究旨在分析 12 例肾移植后隐球菌病患者组织样本中的肉芽肿模式和调节性 T（Treg）免疫反应的原位表达。真菌分离物通过分子鉴定为新型隐球菌种复合体。通过常规组织学检查和对 CD4 和 Treg 标志物：叉头框 P3（FoxP3）、白细胞介素（IL）-10 和转化生长因子（TGF）-β的免疫组织化学检测，对 12 例肾移植后隐球菌病患者的组织样本中的肉芽肿进行了详细描述。肉芽肿分为致密型、疏松型或混合型。与疏松型肉芽肿患者相比，具有混合（n=4）和致密（n=3）肉芽肿性炎症模式的患者预后较好，且 CD4+FoxP3+T 细胞数量更多。相比之下，5 例疏松型肉芽肿患者中有 3 例死于隐球菌病。我们认为，Treg 可能在组织对隐球菌感染的反应中具有保护作用，因为它与预后较好的患者的致密和混合肉芽肿有关。
