Nanjing Maternity and Child Health Care Institute, Nanjing Maternity and Child Health Care Hospital, Women's Hospital of Nanjing Medical University, Nanjing, China.
State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.
Front Immunol. 2021 Jul 22;12:713960. doi: 10.3389/fimmu.2021.713960. eCollection 2021.
Antibiotic resistance has been considered to be a global threat which underscores the need to develop novel anti-infective therapeutics. Modulation of innate immunity by synthetic peptides is an attractive strategy to overcome this circumstance. We recently reported that BCCY-1, a human β-casein-derived peptide displays regulatory activities on monocytes, thereby enhancing their actions in innate immune responses. However, the function of peptide BCCY-1 in host defense against infection remains unknown. In this study, we investigated the characteristics and effects of peptide BCCY-1 in mouse models of bacterial infection. Following intraperitoneal injection, the peptide BCCY-1 exhibited high level of cellular uptake by monocytes without obvious toxicities. Results revealed that peptide BCCY-1, but not the scrambled version, stimulated the chemokine production and monocyte recruitment . Treatment with BCCY-1 enhanced the pathogen clearance and protected mice against lethal infections. Because the anti-infective effects of BCCY-1 was abolished by depletion of monocytes/macrophages rather than lymphocytes and granulocytes, we conclude that monocytes/macrophages are key effector cells in BCCY-1-mediated anti-infective protection. Additionally, BCCY-1 lacks direct antimicrobial activity. To our knowledge, a human β-casein-derived peptide that counters infection by selective regulation of innate immunity has not been reported previously. These results suggest peptide BCCY-1 as a promising alternative approach and a valuable complement to current anti-infective strategy.
抗生素耐药性被认为是一种全球威胁，这凸显了开发新型抗感染治疗方法的必要性。通过合成肽来调节先天免疫是克服这种情况的一种有吸引力的策略。我们最近报道称，一种源自人β-酪蛋白的肽 BCCY-1 对单核细胞具有调节作用，从而增强其在先天免疫反应中的作用。然而，肽 BCCY-1 在宿主抗感染防御中的功能尚不清楚。在这项研究中，我们研究了肽 BCCY-1 在细菌感染小鼠模型中的特性和作用。腹腔注射后，该肽被单核细胞高效摄取，且没有明显的毒性。结果表明，肽 BCCY-1 而非乱序肽可刺激趋化因子的产生和单核细胞的募集。BCCY-1 的治疗增强了病原体的清除，并保护了小鼠免受致死性感染。由于 BCCY-1 的抗感染作用被单核细胞/巨噬细胞耗竭而不是淋巴细胞和粒细胞耗竭所消除，因此我们得出结论，单核细胞/巨噬细胞是 BCCY-1 介导的抗感染保护的关键效应细胞。此外，BCCY-1 没有直接的抗菌活性。据我们所知，以前没有报道过一种通过选择性调节先天免疫来对抗感染的人β-酪蛋白衍生肽。这些结果表明，肽 BCCY-1 是一种很有前途的替代方法，是当前抗感染策略的有价值的补充。
