Intranasal Inoculation of Cryptococcus neoformans in Mice Produces Nasal Infection with Rapid Brain Dissemination
Intranasal Inoculation of Cryptococcus neoformans in Mice Produces Nasal Infection with Rapid Brain Dissemination
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DOI：
10.1128/msphere.00483-19
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发表时间：
2019-07-01
期刊：
影响因子：
4.8
通讯作者：
Casadevall, Arturo
中科院分区：
文献类型：
--
作者：
Coelho, Carolina;Camacho, Emma;Casadevall, Arturo
新型隐球菌是一种重要的真菌病原体，可引起危及生命的肺炎和脑膜脑炎。新型隐球菌的脑传播被认为是肺部活跃感染的结果，然后该感染外渗到其他部位。脑侵入是通过血液中游离酵母细胞的运输或单核吞噬细胞内的特洛伊木马运输传播的结果。我们评估了三种小鼠感染模型的脑传播：静脉内、气管内和鼻内模型。所有三种感染模式均导致新型隐球菌在不到 3 小时内传播至大脑。此外，在小鼠的整个上呼吸道和耳道中均检测到了新型隐球菌。近年来，鼻内感染由于避免了手术而成为诱发肺部感染的流行机制，但我们的研究结果表明，滴注新型隐球菌会产生隐球菌鼻感染。这些发现表明，使用鼻内感染进行的免疫学研究应假设感染的最初感染部位是脑、肺和上呼吸道，包括鼻气道。 重要性 新型隐球菌每年导致估计 181, 000 人死亡，其中大部分与未经治疗的艾滋病毒/艾滋病有关。新型隐球菌在全球范围内广泛分布。人类因暴露于环境来源而受到感染，之后真菌在人体内休眠。在艾滋病引起的免疫抑制或治疗引起的免疫抑制（器官移植受者或患有自身免疫性疾病的患者所需）后，隐球菌疾病会重新激活并导致危及生命的脑膜炎和肺炎。这项研究表明，在与宿主接触后，新型隐球菌可以快速（几个小时）到达宿主大脑，并在受感染动物的鼻子中定殖。因此，这项工作为更好地了解新型隐球菌如何在宿主体内传播铺平了道路。迫切需要了解新型隐球菌如何在宿主体内感染、传播和生存，以便我们能够预防这种致命真菌引起的感染和疾病。
Cryptococcus neoformans is an important fungal pathogen, causing life-threatening pneumonia and meningoencephalitis. Brain dissemination of C. neoformans is thought to be a consequence of an active infection in the lung which then extravasates to other sites. Brain invasion results from dissemination via either transport by free yeast cells in the bloodstream or Trojan horse transport within mononuclear phagocytes. We assessed brain dissemination in three mouse models of infection: intravenous, intratracheal, and intranasal models. All three modes of infection resulted in dissemination of C. neoformans to the brain in less than 3 h. Further, C. neoformans was detected in the entirety of the upper respiratory tract and the ear canals of mice. In recent years, intranasal infection has become a popular mechanism to induce pulmonary infection because it avoids surgery, but our findings show that instillation of C. neoformans produces cryptococcal nasal infection. These findings imply that immunological studies using intranasal infection should assume that the initial sites of infection of infection are brain, lung, and upper respiratory tract, including the nasal airways.IMPORTANCE Cryptococcus neoformans causes an estimated 181, 000 deaths each year, mostly associated with untreated HIV/AIDS. C. neoformans has a ubiquitous worldwide distribution. Humans become infected from exposure to environmental sources, after which the fungus lays dormant within the human body. Upon AIDS-induced immunosuppression or therapy-induced immunosuppression (required for organ transplant recipients or those suffering from autoimmune disorders), cryptococcal disease reactivates and causes life-threatening meningitis and pneumonia. This study showed that upon contact with the host, C. neoformans can quickly (a few hours) reach the host brain and also colonizes the nose of infected animals. Therefore, this work paves the way to better knowledge of how C. neoformans travels through the host body. Understanding how C. neoformans infects, disseminates, and survives within the host is critically required so that we can prevent infections and the disease caused by this deadly fungus.