Innate immune responses play a key role in controlling infection of the intestinal epithelium by Cryptosporidium
Innate immune responses play a key role in controlling infection of the intestinal epithelium by Cryptosporidium
复制标题
DOI：
10.1016/j.ijpara.2017.08.001
复制
发表时间：
2017-10-01
影响因子：
4
通讯作者：
Lacroix-Lamande, Sonia
中科院分区：
文献类型：
--
作者：
Laurent, Fabrice;Lacroix-Lamande, Sonia
隐孢子虫感染导致全球急性腹泻。隐孢子虫病的发生与宿主的免疫状态密切相关，主要影响幼龄反刍动物、婴儿和免疫功能低下的个体。近年来，一些研究提高了我们对负责控制感染急性期的免疫机制的认识，并强调了先天免疫的重要性。寄生虫在肠上皮细胞的顶侧发育，使这些细胞发挥核心作用，因为它们既是寄生虫复制的唯一宿主细胞，又参与保护性免疫反应。上皮细胞通过产生趋化因子来发出感染信号，将免疫细胞吸引到感染区域。它们还通过诱导细胞凋亡和释放具有杀寄生虫活性的游离或并入腔外泌体的抗微生物肽来积极参与宿主防御。寄生虫已经发展了几种逃避机制来减缓这些保护机制。近年来，隐孢子虫三维培养模型的建立以及对隐孢子虫进行基因操作的能力，将为进一步研究宿主-病原体相互作用和鉴定毒力因子提供重要的理论依据。肠上皮细胞需要免疫细胞的帮助来清除感染。肠道树突状细胞以其诱导和协调适应性免疫的能力而闻名，通过充当免疫哨兵和主动效应器在控制隐孢子虫感染的非常早期步骤中发挥关键作用。然而，炎性单核细胞，这是快速和大量招募到感染的粘膜，似乎参与上皮完整性的损失。除了新的有前途的化疗，我们必须考虑刺激新生儿的先天免疫，以加强他们的能力，控制隐孢子虫的发展。微生物群在肠道免疫的发展中起着重要作用，并且可以被认为是宿主-病原体相互作用中的第三个因素。迫切需要减少发展中国家人口中这一控制不力的疾病的发病率，并减少受感染牲畜造成的经济损失。(C)2017作者由Elsevier Ltd代表澳大利亚寄生虫学会出版。
Cryptosporidium infection leads to acute diarrhea worldwide. The development of cryptosporidiosis is closely related to the immune status of its host, affecting primarily young ruminants, infants, and immunocompromised individuals. In recent years, several studies have improved our knowledge on the immune mechanisms responsible for the control of the acute phase of the infection and have highlighted the importance of innate immunity. The parasite develops in the apical side of intestinal epithelial cells, giving these cells a central role, as they are both the exclusive host cell for replication of the parasite and participate in the protective immune response. Epithelial cells signal the infection by producing chemokines, attracting immune cells to the infected area. They also actively participate in host defense by inducing apoptosis and releasing antimicrobial peptides, free or incorporated into luminal exosomes, with parasiticidal activity. The parasite has developed several escape mechanisms to slow down these protective mechanisms. Recent development of several three-dimensional culture models and the ability to genetically manipulate Cryptosporidium will greatly help to further investigate host-pathogen interactions and identify virulence factors. Intestinal epithelial cells require the help of immune cells to clear the infection. Intestinal dendritic cells, well known for their ability to induce and orchestrate adaptive immunity, play a key role in controlling the very early steps of Cryptosporidium parvum infection by acting as immunological sentinels and active effectors. However, inflammatory monocytes, which are quickly and massively recruited to the infected mucosa, seem to participate in the loss of epithelial integrity. In addition to new promising chemotherapies, we must consider stimulating the innate immunity of neonates to strengthen their ability to control Cryptosporidium development. The microbiota plays a fundamental role in the development of intestinal immunity and may be considered to be a third actor in host-pathogen interactions. There is an urgent need to reduce the incidence of this yet poorly controlled disease in the populations of developing countries, and decrease economic losses due to infected livestock. (C) 2017 The Authors. Published by Elsevier Ltd on behalf of Australian Society for Parasitology.