Effect of Pertussis Toxin on Cough in Guinea Pig

描述（由申请人提供）：百日咳博德泰拉是一种革兰氏阴性细菌病原体，引起百日咳或百日咳。被细菌感染呼吸道后，该病的特征是严重和长时间的咳嗽，在症状最严重时经常出现阵发性咳嗽发作，然后在几周或几个月内以较低的频率再次出现。虽然百日咳在本质上是一种人类特有的病原体，但小型实验动物模型，如小鼠和大鼠，已被用于研究百日咳呼吸道感染和疾病的各个方面，各种毒力因素的作用，以及这种感染引起的免疫反应。然而，一个具有代表性的和方便的模型与百日咳疾病相关的咳嗽症状在人类尚未开发。豚鼠是研究咳嗽机制的一个有吸引力的模型，因为它们的咳嗽病理生理学的许多方面，包括引起咳嗽和气道高反应性的刺激，以及气道反应的药理学，与人类咳嗽非常相似。然而，以前没有使用豚鼠来研究百日咳的呼吸道感染。在本提案中概述的研究中，我们的目标是测试使用豚鼠作为与百日咳B.呼吸道感染相关的咳嗽疾病的小动物模型的可行性。特别是，我们将解决百日咳产生的主要毒力因子之一百日咳毒素在引起或改变咳嗽症状中起主要作用的假设。我们的具体目标是：1。目的：阐明百日咳在豚鼠呼吸道的定植特点，包括野生型和百日咳毒素缺陷株；和2。确定豚鼠呼吸道的百日咳感染是否本身引起咳嗽反应，或改变由常用的咳嗽刺激引起的咳嗽病理生理，以及百日咳毒素在这些作用中所起的作用。

DESCRIPTION (provided by applicant): Bordetella pertussis is a gram-negative bacterial pathogen that causes the disease known as pertussis or whooping cough. After respiratory tract infection by the bacteria, the disease is characterized by a severe and prolonged cough, with frequent paroxysmal coughing episodes at the height of the symptoms that then reoccur with reduced frequency over several weeks or months. Although B. pertussis is a human-specific pathogen in nature, small laboratory animal models, such as mice and rats, have been used to study aspects of B. pertussis respiratory tract infection and disease, the role of various virulence factors, and the immune responses elicited to this infection. However, a representative and convenient model for the cough symptoms associated with pertussis disease in humans has not been developed. Guinea pigs represent an attractive model for mechanistic studies on cough, because many aspects of their cough pathophysiology, including the stimuli that elicit cough and airway hyperresponsiveness, and the pharmacology of the airway responses, are very similar to those of human cough. However, guinea pigs have not previously been used to study B. pertussis infection of the respiratory tract. In the study outlined in this proposal, we aim to test the feasibility of using guinea pigs as a small animal model for aspects of the cough disease associated with respiratory tract infection by B. pertussis. In particular, we will address the hypothesis that pertussis toxin, one of the major virulence factors produced by B. pertussis, plays a major role in eliciting or modifying the cough symptomology. Our specific aims are: 1. To elucidate the characteristics of B. pertussis colonization of the guinea pig respiratory tract, including that of wild type and pertussis toxin-deficient strains of B. pertussis; and 2. To determine whether B. pertussis infection of the guinea pig respiratory tract either elicits a cough response itself, or modifies the cough pathophysiology induced by commonly used tussive stimuli, and the role that pertussis toxin plays in these effects.