Pradhan Biswaranjan, Guha Dipanjan, Murmu Krushna Chandra, Sur Abhinav, Ray Pratikshya, Das Debashmita, Aich Palok
School of Biological Sciences, National Institute of Science Education and Research (NISER), HBNI, P.O. Bhimpur-Padanpur, Khurdha, Jatni, Odisha, 752050, India.
J Nanobiotechnology. 2017 Jun 12;15(1):44. doi: 10.1186/s12951-017-0278-1.
Antimicrobial peptides (AMPs) have the potential to serve as an alternative to antibiotic. AMPs usually exert bactericidal activity via direct killing of microbial pathogens. Reports have proposed that by harnessing innate immune activation, AMPs can regulate pathogen invasion and may control infection. It has been reported that AMPs could be utilized to activate the innate mucosal immune response in order to eliminate pathogenic infections. This way of controlling pathogen infection, by activating host immunity, confers the potential to the select AMPs to alleviate the problem of antibiotic resistance. Among various AMPs tested LL-37 and indolicidin, showed promise to be potential candidates for eliciting enhanced host innate immune responses. LL-37 and indolicidin had exhibited substantial innate immune activation in both human and murine macrophages. Dosage for each of the AMPs, however, was high with adverse side effects.
In this study, we reported that upon conjugation with carbon nanotubes (CNT), each AMP remained biologically functional at a concentration that was 1000-fold less than the dosage required for free AMP to remain active in the cells.
Current study also revealed that while indolicidin induced signalling events mediated through the TNFRSF1A pathway in THP1 cells, followed by activation of NFκB and c-JUN pathways, treatment of cells with LL-37 induced signalling events by activating IL1R, with subsequent activation of NFκB and NFAT2. Thp1 cells, primed with CNT conjugated LL-37 or indolicidin, are protected against Salmonella typhimurium infection at 16 h post challenge.
抗菌肽（AMPs）有潜力成为抗生素的替代品。抗菌肽通常通过直接杀死微生物病原体发挥杀菌活性。有报道提出，通过利用先天免疫激活，抗菌肽可以调节病原体入侵并可能控制感染。据报道，抗菌肽可用于激活先天黏膜免疫反应以消除致病性感染。这种通过激活宿主免疫来控制病原体感染的方式，赋予了所选抗菌肽缓解抗生素耐药性问题的潜力。在测试的各种抗菌肽中，LL-37和吲哚杀菌素有望成为引发增强宿主先天免疫反应的潜在候选者。LL-37和吲哚杀菌素在人类和小鼠巨噬细胞中均表现出显著的先天免疫激活。然而，每种抗菌肽的剂量都很高且有不良副作用。
在本研究中，我们报道了与碳纳米管（CNT）结合后，每种抗菌肽在浓度比游离抗菌肽在细胞中保持活性所需剂量低1000倍的情况下仍保持生物学功能。
当前研究还表明，虽然吲哚杀菌素在THP1细胞中诱导通过TNFRSF1A途径介导的信号事件，随后激活NFκB和c-JUN途径，但用LL-37处理细胞通过激活IL1R诱导信号事件，随后激活NFκB和NFAT2。用CNT结合的LL-37或吲哚杀菌素预处理的Thp1细胞在受到攻击后16小时可免受鼠伤寒沙门氏菌感染。
