摘要
With the growing problem of the emergence of antibiotic-resistant bacteria, the search for alternative ways to combat bacterial infections is extremely urgent. While analyzing the effect of antimicrobial peptides (AMPs) on immunocompetent cells, their effect on all parts of the immune system, and on humoral and cellular immunity, is revealed. AMPs have direct effects on neutrophils, monocytes, dendritic cells, T-lymphocytes, and mast cells, participating in innate immunity. They act on B-lymphocytes indirectly, enhancing the induction of antigen-specific immunity, which ultimately leads to the activation of adaptive immunity. The adjuvant activity of AMPs in relation to bacterial and viral antigens was the reason for their inclusion in vaccines and made it possible to formulate the concept of a “defensin vaccine” as an innovative basis for constructing vaccines. The immunomodulatory function of AMPs involves their influence on cells in the nearest microenvironment, recruitment and activation of other cells, supporting the response to pathogenic microorganisms and completing the inflammatory process, thus exhibiting a systemic effect. For the successful use of AMPs in medical practice, it is necessary to study their immunomodulatory activity in detail, taking into account their pleiotropy. The degree of maturity of the immune system and microenvironment can contribute to the prevention of complications and increase the effectiveness of therapy, since AMPs can suppress inflammation in some circumstances, but aggravate the response and damage of organism in others. It should also be taken into account that the real functions of one or another AMP depend on the types of total regulatory effects on the target cell, and not only on properties of an individual peptide. A wide spectrum of biological activity, including direct effects on pathogens, inactivation of bacterial toxins and influence on immunocompetent cells, has attracted the attention of researchers, however, the cytostatic activity of AMPs against normal cells, as well as their allergenic properties and low stability to host proteases, are serious limitations for the medical use of AMPs. In this connection, the tasks of searching for compounds that selectively affect the target and development of an appropriate method of application become critically important. The scope of this review is to summarize the current concepts and newest advances in research of the immunomodulatory activity of natural and synthetic AMPs, and to examine the prospects and limitations of their medical use.
摘要译文
随着抗生素耐药细菌出现的日益严重的问题，寻找对抗细菌感染的替代方法非常紧迫。在分析抗菌肽（AMP）对免疫能力细胞的影响时，揭示了它们对免疫系统所有部位以及对体液和细胞免疫的影响。放大器对中性粒细胞，单核细胞，树突状细胞，T淋巴细胞和肥大细胞有直接影响，参与先天免疫。它们间接作用于B淋巴细胞，增强了抗原特异性免疫的诱导，最终导致适应性免疫的激活。 AMP与细菌和病毒抗原有关的辅助活性是它们纳入疫苗的原因，并使得制定“防御素疫苗”的概念作为构建疫苗的创新基础。 AMP的免疫调节功能涉及它们对最近微环境，其他细胞的募集和激活中对细胞的影响，支持对病原微生物的反应并完成炎症过程，从而表现出系统性效应。为了成功地在医学实践中使用AMP，有必要考虑其多效性，以详细研究其免疫调节活性。免疫系统和微环境的成熟程度可以有助于预防并发症并提高治疗的有效性，因为AMP在某些情况下会抑制炎症，但会加剧其他有机体的反应和损害。还应考虑到一个或另一个放大器的实际功能取决于对目标细胞的总调节作用的类型，而不仅取决于单个肽的特性。但是，广泛的生物学活性，包括对病原体的直接影响，细菌毒素的失活以及对免疫能力细胞的影响，吸引了研究人员的注意，但是，AMP对正常细胞的细胞抑制活性以及它们的过敏性和低稳定性托管蛋白酶是对AMP的医疗使用的严重局限性。在这方面，搜索选择性影响目标和开发适当应用方法的化合物的任务至关重要。这篇综述的范围是总结自然和合成放大器免疫调节活性研究的当前概念和最新进展，并检查其医疗使用的前景和局限性。
Svetlana V. Guryanova;Tatiana V. Ovchinnikova. Immunomodulatory and Allergenic Properties of Antimicrobial Peptides[J]. International Journal of Molecular Sciences, 2022,23(5): 2499