In the last decade, the paradigm of primary immunodeficiencies (PIDs) as rare recessive familial diseases that lead to broad, severe, and early‐onset immunological defects has shifted toward collectively more common, but sporadic autosomal dominantly inherited isolated defects in the immune response. Patients with PIDs constitute a formidable area of research to study the genetics and the molecular mechanisms of complex immunological pathways. A significant subset of PIDs affect the innate immune response, which is a crucial initial host defense mechanism equipped with pattern‐recognition receptors. These receptors recognize pathogen‐ and damage‐associated molecular patterns in both the extracellular and intracellular space. In this review, we will focus on primary immunodeficiencies caused by genetic defects in cytosolic pattern‐recognition receptor pathways. We discuss these PIDs organized according to their mutational mechanisms and consequences for the innate host response. The advanced understanding of these pathways obtained by the study of PIDs creates the opportunity for the development of new host‐directed treatment strategies.

中文翻译：

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细胞溶质模式识别受体通路中的原发性免疫缺陷：针对宿主的治疗策略。

在过去的十年中，原发性免疫缺陷 (PID) 作为罕见的隐性家族性疾病，导致广泛、严重和早发性免疫缺陷的范式已经转变为更常见但散发性的常染色体显性遗传免疫反应中的孤立缺陷。PID 患者是研究复杂免疫通路的遗传学和分子机制的重要研究领域。PID 的一个重要子集影响先天免疫反应，这是配备模式识别受体的关键初始宿主防御机制。这些受体识别细胞外和细胞内空间中的病原体和损伤相关分子模式。在这次审查中，我们将关注由细胞溶质模式识别受体通路中的遗传缺陷引起的原发性免疫缺陷。我们讨论根据其突变机制和先天宿主反应的后果组织的这些 PID。通过对 PID 的研究获得对这些途径的深入了解，为开发新的宿主导向治疗策略创造了机会。