CINDEFI (UNLP CONICET La Plata), Facultad de Ciencias Exactas, Universidad Nacional de La Plata, La Plata, Argentina.
Infect Immun. 2012 Dec;80(12):4309-16. doi: 10.1128/IAI.00662-12. Epub 2012 Oct 1.
Whooping cough is a reemerging disease caused by two closely related pathogens, Bordetella pertussis and Bordetella parapertussis. The incidence of B. parapertussis in whooping cough cases has been increasing since the introduction of acellular pertussis vaccines containing purified antigens that are common to both strains. Recently published results demonstrated that these vaccines do not protect against B. parapertussis due to the presence of the O antigen on the bacterial surface that impairs antibody access to shared antigens. We have investigated the effect of the lack of opsonization of B. parapertussis on the outcome of its interaction with human neutrophils (polymorphonuclear leukocytes [PMNs]). In the absence of opsonic antibodies, PMN interaction with B. parapertussis resulted in nonbactericidal trafficking upon phagocytosis. A high percentage of nonopsonized B. parapertussis was found in nonacidic lysosome marker (lysosome-associated membrane protein [LAMP])-negative phagosomes with access to the host cell-recycling pathway of external nutrients, allowing bacterial survival as determined by intracellular CFU counts. The lipopolysaccharide (LPS) O antigen was found to be involved in directing B. parapertussis to PMN lipid rafts, eventually determining the nonbactericidal fate inside the PMN. IgG opsonization of B. parapertussis drastically changed this interaction by not only inducing efficient PMN phagocytosis but also promoting PMN bacterial killing. These data provide new insights into the immune mechanisms of hosts against B. parapertussis and document the crucial importance of opsonic antibodies in immunity to this pathogen.
百日咳是一种由两种密切相关的病原体引起的重新出现的疾病,即百日咳博德特氏菌和副百日咳博德特氏菌。自从含有两种菌株共同抗原的无细胞百日咳疫苗问世以来,副百日咳博德特氏菌在百日咳病例中的发病率一直在上升。最近发表的结果表明,由于细菌表面存在 O 抗原,这些疫苗不能预防副百日咳,因为该抗原会阻碍抗体与共同抗原的结合。我们研究了副百日咳博德特氏菌缺乏调理作用对其与人中性粒细胞(多形核白细胞[PMN])相互作用结果的影响。在缺乏调理抗体的情况下,PMN 与副百日咳博德特氏菌的相互作用导致吞噬后非杀菌性运输。在非酸性溶酶体标志物(溶酶体相关膜蛋白[LAMP])阴性吞噬体中发现大量未被调理的副百日咳博德特氏菌,这些吞噬体可进入宿主细胞的外部营养物质再循环途径,从而使细菌得以存活,这可通过细胞内 CFU 计数来确定。发现脂多糖(LPS)O 抗原参与指导副百日咳博德特氏菌进入 PMN 脂筏,最终决定 PMN 内的非杀菌命运。副百日咳博德特氏菌的 IgG 调理作用不仅可以诱导有效的 PMN 吞噬作用,而且可以促进 PMN 杀菌,从而极大地改变了这种相互作用。这些数据为宿主针对副百日咳博德特氏菌的免疫机制提供了新的见解,并证明调理抗体在针对这种病原体的免疫中至关重要。