Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Allergy. 2012 Oct;67(10):1250-8. doi: 10.1111/j.1398-9995.2012.02884.x. Epub 2012 Aug 22.
We previously reported that prior nasal administration of highly attenuated Bordetella pertussis BPZE1 provides effective and sustained protection against lethal challenge with influenza A viruses. The protective effect was mediated by suppressing the production of major pro-inflammatory mediators. To further explore the anti-inflammatory properties of BPZE1, we investigated the effect of BPZE1 nasal pretreatment on two mouse models of allergic disease, allergic airway inflammation, and contact hypersensitivity (CHS).
Allergic reactions were induced in mice nasally pretreated with live attenuated BPZE1 bacteria using the ovalbumin (OVA)-induced allergic airway inflammation and dinitrochlorobenzene (DNCB)-induced CHS models.
Prior BPZE1 nasal treatment suppressed OVA-induced lung inflammation and inflammatory cell recruitment and significantly reduced IgE levels and cytokine production. Similarly, BPZE1 nasal pretreatment markedly inhibited ear swelling, skin inflammation, and production of pro-inflammatory cytokines in the DNCB-induced CHS model. For both models, we showed that BPZE1 pretreatment does not affect the sensitization phase. Upon challenge, BPZE1 pretreatment selectively reduced the level of cytokines whose production is increased and did not affect the basal level of other cytokines. Together, our observations suggest that BPZE1 pretreatment specifically targets those cytokine-producing effector cells that are recruited and involved in the inflammatory reaction.
Our study demonstrates the broad anti-inflammatory properties of the attenuated B. pertussis BPZE1 vaccine candidate and supports its development as a promising agent to prevent and/or treat allergic diseases.
我们之前报道过,先前经鼻腔给予高度减毒的百日咳博德特氏菌 BPZE1 可有效且持续地预防流感 A 病毒的致死性攻击。这种保护作用是通过抑制主要促炎介质的产生来介导的。为了进一步探索 BPZE1 的抗炎特性,我们研究了 BPZE1 鼻腔预处理对两种过敏性疾病模型,即过敏性气道炎症和接触性超敏反应 (CHS) 的影响。
使用卵清蛋白 (OVA) 诱导的过敏性气道炎症和二硝基氯苯 (DNCB) 诱导的 CHS 模型,对经活减毒 BPZE1 细菌鼻腔预处理的小鼠进行过敏性反应诱导。
BPZE1 鼻腔预处理抑制了 OVA 诱导的肺部炎症和炎症细胞募集,并显著降低了 IgE 水平和细胞因子产生。同样,BPZE1 鼻腔预处理也显著抑制了 DNCB 诱导的 CHS 模型中耳朵肿胀、皮肤炎症和促炎细胞因子的产生。对于这两种模型,我们表明 BPZE1 预处理不影响致敏阶段。在受到挑战时,BPZE1 预处理选择性地降低了那些增加的细胞因子的水平,而不影响其他细胞因子的基础水平。总之,我们的观察结果表明,BPZE1 预处理特异性针对那些募集并参与炎症反应的细胞因子产生效应细胞。
我们的研究表明,减毒百日咳博德特氏菌 BPZE1 候选疫苗具有广泛的抗炎特性,并支持其作为预防和/或治疗过敏性疾病的有前途的药物的开发。