Eby Joshua C, Hoffman Casandra L, Gonyar Laura A, Hewlett Erik L
Division of Infectious Diseases, University of Virginia, Charlottesville, VA 22908, USA
Division of Infectious Diseases, University of Virginia, Charlottesville, VA 22908, USA.
Pathog Dis. 2015 Dec;73(9):ftv081. doi: 10.1093/femspd/ftv081. Epub 2015 Oct 2.
The nature and timing of the neutrophil response to infection with Bordetella pertussis is influenced by multiple virulence factors expressed by the bacterium. After inoculation of the host airway, the recruitment of neutrophils signaled by B. pertussis lipooligosaccharide (LOS) is suppressed by pertussis toxin (PTX). Over the next week, the combined activities of PTX, LOS and adenylate cyclase toxin (ACT) result in production of cytokines that generate an IL-17 response, promoting neutrophil recruitment which peaks at 10-14 days after inoculation in mice. Arriving at the site of infection, neutrophils encounter the powerful local inhibitory activity of ACT, in conjunction with filamentous hemagglutinin. With the help of antibodies, neutrophils contribute to clearance of B. pertussis, but only after 28-35 days in a naïve mouse. Studies of the lasting, antigen-specific IL-17 response to infection in mice and baboons has led to progress in vaccine development and understanding of pathogenesis. Questions remain about the mediators that coordinate neutrophil recruitment and the mechanisms by which neutrophils overcome B. pertussis virulence factors.
中性粒细胞对百日咳博德特氏菌感染的反应性质和时间受到该细菌表达的多种毒力因子的影响。在接种至宿主气道后,百日咳博德特氏菌脂寡糖(LOS)所引发的中性粒细胞募集会被百日咳毒素(PTX)抑制。在接下来的一周内,PTX、LOS和腺苷酸环化酶毒素(ACT)的共同作用会导致细胞因子的产生,从而引发白细胞介素-17反应,促进中性粒细胞募集,在小鼠接种后10 - 14天达到峰值。到达感染部位后,中性粒细胞会遇到ACT与丝状血凝素共同产生的强大局部抑制活性。在抗体的帮助下,中性粒细胞有助于清除百日咳博德特氏菌,但在未接触过该菌的小鼠中,这一过程要在28 - 35天后才会发生。对小鼠和狒狒感染后持久的、抗原特异性白细胞介素-17反应的研究推动了疫苗开发及对发病机制的理解。关于协调中性粒细胞募集的介质以及中性粒细胞克服百日咳博德特氏菌毒力因子的机制仍存在疑问。