Gaultier Gabrielle N, Colledanchise Kayla N, Alhazmi Alaa, Ulanova Marina
Department of Biology, Lakehead University, Thunder Bay, ON, Canada.
Northern Ontario School of Medicine, Thunder Bay, ON, Canada.
Pathog Immun. 2017 Feb 16;2(1):34-49. doi: 10.20411/pai.v2i1.162. eCollection 2017.
We have recently found that lipooligosaccharide (LOS) isolated from encapsulated strains of () has strong adjuvant, but diminished pro-inflammatory ability as compared to lipopolysaccharide (LPS). In this study, we aimed to determine the immunostimulatory capacity of nontypeable/ non-encapsulated (NTHi) LOS by comparing the effect of killed bacteria with LOS isolated from the same strain.
Following stimulation of human monocytic THP-1 cells with killed NTHi strain 375, or with the corresponding amount of LOS, we studied the protein and gene expression of immunostimulatory and antigen-presenting molecules, cytokines, and innate immune receptors.
Stimulation with LOS resulted in lower expression of adhesion (CD54, CD58) as well as costimulatory molecules (CD40, CD86), but in higher expression of antigen-presenting molecules (HLA-DR and HLA-ABC) compared to killed NTHi, whereas killed bacteria induced higher release of both TNF-α and IL-10. The results indicate that while LOS of NTHi has decreased capacity to induce pro-inflammatory responses compared to LPS or killed NTHi, this LOS has the potential to facilitate antigen presentation.
Considering the important role of NTHi as a respiratory pathogen, and its currently increasing significance in the etiology of invasive infections, LOS deserves further attention as a vaccine antigen, which also has potent adjuvant properties.
我们最近发现,从()的包膜菌株中分离出的脂寡糖(LOS)具有很强的佐剂作用,但与脂多糖(LPS)相比,其促炎能力有所减弱。在本研究中,我们旨在通过比较死菌与从同一菌株分离出的LOS的作用,来确定不可分型/无包膜的(NTHi)LOS的免疫刺激能力。
用人单核细胞THP-1细胞分别用死的NTHi菌株375或相应量的LOS刺激后,我们研究了免疫刺激和抗原呈递分子、细胞因子和先天免疫受体的蛋白质和基因表达。
与死的NTHi相比,用LOS刺激导致黏附分子(CD54、CD58)以及共刺激分子(CD40、CD86)的表达较低,但抗原呈递分子(HLA-DR和HLA-ABC)的表达较高,而死菌诱导TNF-α和IL-10的释放更高。结果表明,虽然与LPS或死的NTHi相比,NTHi的LOS诱导促炎反应的能力有所下降,但这种LOS有促进抗原呈递的潜力。
考虑到NTHi作为呼吸道病原体的重要作用,以及其目前在侵袭性感染病因学中的重要性日益增加,LOS作为一种具有强大佐剂特性的疫苗抗原值得进一步关注。