What Causes the Cough in Whooping Cough?

Area of Science:

• Microbiology
• Immunology
• Pathophysiology

Background:

• The precise cause of the severe cough in whooping cough (pertussis) has remained elusive due to limited small animal models.
• Understanding the interplay between bacterial virulence factors and host responses is crucial for explaining pertussis pathophysiology.

Purpose of the Study:

• To investigate the bacterial and host factors responsible for cough production during Bordetella pertussis infection.
• To elucidate the mechanisms underlying the severe, debilitating cough associated with pertussis.

Main Methods:

• Utilized a mouse model of Bordetella pertussis infection.
• Conducted cellular studies to identify key bacterial and host interactions.
• Analyzed the role of specific bacterial toxins and host signaling pathways.

Main Results:

• Pertussis toxin, lipooligosaccharide, and Vag8 were identified as cooperative bacterial factors inducing cough.
• These bacterial factors stimulate the production of host bradykinin, a potent cough inducer.
• Bacterial factors were shown to alter host signaling pathways, exacerbating cough responses via TRPV1 sensitization.

Conclusions:

• Bacterial factors and host bradykinin signaling are critical in driving the severe cough of pertussis.
• This research provides a mechanistic understanding of pertussis-induced cough.
• Findings may inform the development of novel therapeutic strategies targeting cough in pertussis patients.