Arnaiz-Villena Antonio, Juarez Ignacio, Vaquero-Yuste Christian, Lledo Tomás, Martin-Villa José Manuel, Suarez-Trujillo Fabio
Department of Immunology, School of Medicine, Complutense University of Madrid, 28040 Madrid, Spain.
Instituto de Investigacion Sanitaria Gegorio Marañon, 28009 Madrid, Spain.
Biomedicines. 2024 Aug 22;12(8):1928. doi: 10.3390/biomedicines12081928.
The relationship between microbiota and the immune system is complex and characterized by the ways in which microbiota directs immune function interactions, both innate and acquired and also keeps activating the immune system throughout an individual's life. In this respect, the human Major Histocompatibility Complex (MHC, referred to as HLA in humans) plays a crucial role and is also established in self-defense against microbes by presenting microbial-derived peptides to the immune cells. However, this assumption has some unclear aspects that should be investigated. For example, how is the microbiota shaped by microbe species diversity, quantity and functions of the immune system, as well as the role and molecular mechanisms of the HLA complex during this process. There are autoimmune diseases related to both HLA and specific microbiota changes or alterations, many of which are mentioned in the present review. In addition, the HLA peptide presenting function should be put in a framework together with its linkage to diseases and also with HLA compatibility necessary for transplants to be successful. These are still quite an enigmatically statistical and phenomenological approach, but no firm pathogenic mechanisms have been described; thus, HLA's real functioning is still to be fully unveiled. After many years of HLA single-genes studies, firm pathogenesis mechanisms underlying disease linkage have been discovered. Finally, microbiota has been defined as conformed by bacteria, protozoa, archaea, fungi, and viruses; notwithstanding, endogenous viral sequences integrated into the human genome and other viral particles (obelisks) recently found in the digestive mucosa should be taken into account because they may influence both the microbiome and the immune system and their interactions. In this context, we propose to integrate these microbial-genetic particle components into the microbiome concept and designate it as "microgenobiota".
微生物群与免疫系统之间的关系十分复杂，其特点在于微生物群指导先天免疫和后天免疫功能相互作用的方式，并且在个体的一生中持续激活免疫系统。在这方面，人类主要组织相容性复合体（MHC，在人类中称为HLA）发挥着关键作用，它通过向免疫细胞呈递微生物衍生肽在抵御微生物的自我防御中也得以确立。然而，这一假设存在一些尚待研究的不明确之处。例如，微生物群是如何受到微生物物种多样性、免疫系统的数量和功能的影响而形成的，以及在此过程中HLA复合体的作用和分子机制。存在与HLA和特定微生物群变化或改变相关的自身免疫性疾病，本综述中提及了其中许多疾病。此外，HLA肽呈递功能应与它与疾病的关联以及移植成功所需的HLA相容性一同置于一个框架中考虑。这些仍然是一种相当神秘的统计和现象学方法，但尚未描述确切的致病机制；因此，HLA的实际功能仍有待全面揭示。经过多年对HLA单基因的研究，已经发现了疾病关联背后的确切发病机制。最后，微生物群已被定义为由细菌、原生动物、古细菌、真菌和病毒组成；尽管如此，应考虑整合到人类基因组中的内源性病毒序列以及最近在消化黏膜中发现的其他病毒颗粒（类病毒颗粒），因为它们可能影响微生物群和免疫系统及其相互作用。在此背景下，我们建议将这些微生物 - 遗传颗粒成分整合到微生物群概念中，并将其命名为“微基因微生物群”。
