过敏性气道致敏作用会损害细菌性呼吸道感染期间的抗菌IgG抗体反应

2018/09/10

   摘要
   背景:肺炎支原体(Mpn)是一种非典型的人类病原体,与哮喘的发生和恶化有关。据报道,与非哮喘患者相比,哮喘患者的Mpn携带率更高,并且患有侵袭性呼吸道感染的风险更高。本文旨在研究之前过敏原致敏是否影响宿主对慢性细菌感染的反应。
   方法:BALB/cJ和IL-4Rα-/-小鼠用卵清蛋白(OVA)致敏,然后用Mpn或肺炎链球菌(Spn)感染。在感染后30天分析免疫参数,并包括支气管肺泡灌洗(BAL)中的细胞分类,以及针对全细菌裂解物,重组P1(rP1)粘附素和OVA的血清IgG和IgE抗体水平。检查总肺RNA的转录水平和BAL液的细胞因子蛋白质谱。
   结果:与对照组相比,过敏原致敏的Mpn感染动物的抗Mpn抗体应答降低,但OVA特异性IgG应答未受影响。相似地,在OVA致敏的动物中发现抗Spn抗体水平也出现降低。然而,Mpn,但不是Spn,感染增强了抗OVA IgE抗体反应。在IgG2a和IgG2b亚类中,IL-4受体信号传导的丧失部分恢复了抗Mpn抗体反应。与未感染的OVA致敏对照相比,OVA致敏Mpn或Spn感染动物的BAL液中的炎性细胞因子水平降低。出乎意料的是,在Mpn感染的OVA致敏动物中,基本上消除了对乙酰甲胆碱的气道高反应性。
   结论:Th2型宿主免疫反应很大程度上以不依赖病原体的方式损害宿主对呼吸道细菌感染的免疫应答。一些病原体(例如Mpn)可以增强持续的过敏反应并抑制肺Th2细胞因子反应和过敏性气道高反应性。
 
 
(中日友好医院呼吸与危重症医学科 王瑞茵 摘译 林江涛 审校)
(J Allergy Clin Immunol. 2018 Aug 6. pii: S0091-6749(18)31128-X.)

 
 
 
Allergic Airway Sensitization Impairs Anti-Bacterial IgG Antibody Responses During Bacterial Respiratory Infections.
 
Totten AH, Xiao L, Luo D, Briles D, Hale JY, Crabb DM, Schoeb TR, Alishlash AS, Waites KB, Atkinson TP.
 
Abstract
BACKGROUND:Mycoplasma pneumoniae (Mpn), an atypical human pathogen, has been associated with asthma initiation and exacerbation. Asthmatics have been reported to have higher carriage rates of Mpn compared to non-asthmatics, and are at greater risk for invasive respiratory infections. To study whether prior allergen sensitization affects the host response to chronic bacterial infection.
METHODS:BALB/cJ and IL-4Rα-/- mice were sensitized with ovalbumin (OVA), and then infected with Mpn or Streptococcus pneumoniae (Spn). Immune parameters were analyzed at 30 days post-infection and included cellular profiles in bronchoalveolar lavage (BAL), and serum IgG and IgE antibody levels to whole bacterial lysate, recombinant P1 (rP1) adhesin, and OVA. Total lung RNA was examined for transcript levels and BAL fluid for cytokine protein profiles.
RESULTS:Anti-Mpn antibody responses were decreased in allergen-sensitized, Mpn-infected animals compared to controls, but OVA-specific IgG responses were unaffected. Similar decreases in anti-Spn antibody levels were found in OVA-sensitized animals. However, Mpn, but not Spn, infection augmented anti-OVA IgE antibody responses. Loss of IL-4 receptor signaling partially restored anti-Mpn antibody responses in IgG2a and IgG2b subclasses. Inflammatory cytokine levels in BAL fluid from OVA-sensitized, Mpn- or Spn-infected animals were reduced compared to uninfected OVA-sensitized controls. Unexpectedly, airway hyperreactivity to methacholine was essentially ablated in Mpn-infected, OVA-sensitized animals.
CONCLUSIONS:An established Type 2-biased host immune response impairs the host immune response to respiratory bacterial infection in a largely pathogen independent manner. Some pathogens, e.g. Mpn, can augment ongoing allergic responses and inhibit pulmonary T2 cytokine responses and allergic airway hyperreactivity.




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