Kraaij Marina D, van Dijk Albert, Scheenstra Maaike R, van Harten Roel M, Haagsman Henk P, Veldhuizen Edwin J A
Division of Molecular Host Defence, Department of Infectious Diseases & Immunology, Utrecht University, Utrecht, Netherlands.
Protein Pept Lett. 2020;27(1):60-66. doi: 10.2174/0929866526666190730125525.
Cathelicidins are a family of Host Defense Peptides (HDPs), that play an important role in the innate immune response. They exert both broad-spectrum antimicrobial activity against pathogens, and strong immunomodulatory functions that affect the response of innate and adaptive immune cells.
The aim of this study was to investigate immunomodulation by the chicken cathelicidin CATH-2 and compare its activities to those of the human cathelicidin LL-37.
Chicken macrophages and chicken monocytes were incubated with cathelicidins. Activation of immune cells was determined by measuring surface markers Mannose Receptor Ctype 1 (MRC1) and MHC-II. Cytokine production was measured by qPCR and nitric oxide production was determined using the Griess assay. Finally, the effect of cathelicidins on phagocytosis was measured using carboxylate-modified polystyrene latex beads.
CATH-2 and its all-D enantiomer D-CATH-2 increased MRC1 and MHC-II expression, markers for antigen presentation, on primary chicken monocytes, whereas LL-37 did not. D-CATH- 2 also increased the MRC1 and MHC-II expression if a chicken macrophage cell line (HD11 cells) was used. In addition, LPS-induced NO production by HD11 cells was inhibited by CATH-2 and D-CATH-2.
These results are a clear indication that CATH-2 (and D-CATH-2) affect the activation state of monocytes and macrophages, which leads to optimization of the innate immune response and enhancement of the adaptive immune response.
杀菌肽是一类宿主防御肽(HDPs),在先天免疫反应中发挥重要作用。它们对病原体具有广谱抗菌活性,并具有强大的免疫调节功能,可影响先天免疫细胞和适应性免疫细胞的反应。
本研究旨在探讨鸡杀菌肽CATH-2的免疫调节作用,并将其活性与人类杀菌肽LL-37的活性进行比较。
将鸡巨噬细胞和鸡单核细胞与杀菌肽一起孵育。通过测量表面标志物甘露糖受体C型1(MRC1)和MHC-II来确定免疫细胞的激活情况。通过qPCR测量细胞因子的产生,并使用格里斯试剂法测定一氧化氮的产生。最后,使用羧酸盐修饰的聚苯乙烯乳胶珠测量杀菌肽对吞噬作用的影响。
CATH-2及其全D对映体D-CATH-2可增加原代鸡单核细胞上抗原呈递标志物MRC1和MHC-II的表达,而LL-37则无此作用。如果使用鸡巨噬细胞系(HD11细胞),D-CATH-2也会增加MRC1和MHC-II的表达。此外,CATH-2和D-CATH-2可抑制HD11细胞中LPS诱导的一氧化氮产生。
这些结果清楚地表明,CATH-2(和D-CATH-2)会影响单核细胞和巨噬细胞的激活状态,从而导致先天免疫反应的优化和适应性免疫反应的增强。