Studies of vertebrate immunity have traditionally focused on professional cells, including circulating and tissue-resident leukocytes. Evidence that non-professional cells are also intrinsically essential (i.e. not via their effect on leukocytes) for protective immunity in natural conditions of infection has emerged from three lines of research in human genetics. First, studies of Mendelian resistance to infection have revealed an essential role of DARC-expressing erythrocytes in protection against Plasmodium vivax infection, and an essential role of FUT2-expressing intestinal epithelial cells for protection against norovirus and rotavirus infections. Second, studies of inborn errors of non-hematopoietic cell-extrinsic immunity have shown that APOL1 and complement cascade components secreted by hepatocytes are essential for protective immunity to trypanosome and pyogenic bacteria, respectively. Third, studies of inborn errors of non-hematopoietic cell-intrinsic immunity have suggested that keratinocytes, pulmonary epithelial cells, and cortical neurons are essential for tissue-specific protective immunity to human papillomaviruses, influenza virus, and herpes simplex virus, respectively. Various other types of genetic resistance or predisposition to infection in human populations are not readily explained by inborn variants of genes operating in leukocytes and may, therefore, involve defects in other cells. The probing of this unchartered territory by human genetics is reshaping immunology, by scaling immunity to infection up from the immune system to the whole organism.

中文翻译：

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人类对感染的先天免疫错误影响白细胞以外的细胞：从免疫系统到整个有机体。


脊椎动物免疫的研究传统上集中于专业细胞，包括循环和组织驻留白细胞。人类遗传学的三项研究已经证明，在自然感染条件下，非专业细胞对于保护性免疫也具有本质上的必要性（即不是通过它们对白细胞的影响）。首先，孟德尔抗感染性研究揭示了表达 DARC 的红细胞在预防间日疟原虫感染中的重要作用，以及表达 FUT2 的肠上皮细胞在预防诺如病毒和轮状病毒感染中的重要作用。其次，对非造血细胞外源性免疫先天性缺陷的研究表明，肝细胞分泌的APOL1和补体级联成分分别对于锥虫和化脓性细菌的保护性免疫至关重要。第三，对非造血细胞固有免疫先天性缺陷的研究表明，角质形成细胞、肺上皮细胞和皮质神经元分别对于人乳头瘤病毒、流感病毒和单纯疱疹病毒的组织特异性保护性免疫至关重要。人类群体中各种其他类型的遗传抗性或感染倾向不容易用白细胞中运行的基因的先天变异来解释，因此可能涉及其他细胞的缺陷。人类遗传学对这一未知领域的探索正在重塑免疫学，将感染免疫力从免疫系统扩展到整个有机体。