Laboratory of Pediatrics, Division of Pediatric Infectious Diseases and Immunology, Erasmus MC-Sophia Children's Hospital, University Medical Center, Rotterdam, The Netherlands.
Department of Pediatrics, Division of Pediatric Infectious Diseases and Immunology, Erasmus MC-Sophia Children's Hospital, University Medical Center, Rotterdam, The Netherlands.
Infect Immun. 2019 Jan 24;87(2). doi: 10.1128/IAI.00663-18. Print 2019 Feb.
Antibody responses to correlate with pulmonary clearance. However, -specific IgG antibodies can cross-react with the myelin glycolipid galactocerebroside (GalC) and cause neurological disorders. We assessed whether antiglycolipid antibody formation is part of the physiological immune response to We show that antibodies against proteins and glycolipids arise in serum of -infected children and mice. Although antibodies to glycolipids were mainly IgG, anti-GalC antibodies were only IgM. B-1a cells, shown to aid in protection against pathogen-derived glycolipids, are lacking in Bruton tyrosine kinase (Btk)-deficient mice. -infected Btk-deficient mice developed -specific IgG responses to proteins but not to glycolipids, including GalC. The equal recovery from infection in Btk-deficient and wild-type mice suggests that pulmonary clearance is predominantly mediated by IgG reactive with proteins and that glycolipid-specific IgG or IgM is not essential. These data will guide the development of -targeting vaccines that avoid the induction of neurotoxic antibodies.
针对肺炎支原体的抗体反应与肺部清除能力相关。然而,肺炎支原体特异性 IgG 抗体可能与髓鞘糖脂半乳糖脑苷脂(GalC)发生交叉反应,导致神经紊乱。我们评估了抗糖脂抗体的形成是否是针对肺炎支原体的生理性免疫反应的一部分。我们发现,针对肺炎支原体蛋白和糖脂的抗体出现在感染肺炎支原体的儿童和小鼠的血清中。虽然针对肺炎支原体糖脂的抗体主要是 IgG,但抗 GalC 抗体仅为 IgM。B-1a 细胞被证明有助于抵御病原体衍生的糖脂,而 Bruton 酪氨酸激酶(Btk)缺陷型小鼠中缺乏这种细胞。感染肺炎支原体的 Btk 缺陷型小鼠产生了针对肺炎支原体蛋白的特异性 IgG 反应,但不产生针对肺炎支原体糖脂的反应,包括 GalC。Btk 缺陷型和野生型小鼠从肺炎支原体感染中同等程度地恢复,这表明肺部清除主要由与肺炎支原体蛋白反应的 IgG 介导,而针对肺炎支原体糖脂的 IgG 或 IgM 并非必需。这些数据将指导针对肺炎支原体的疫苗的开发,避免诱导神经毒性抗体。