What Causes the Cough in Whooping Cough?

What causes the cough in whooping cough (pertussis) has been a longstanding question in the field but has been difficult to answer because of the perceived lack of convenient small animal models. Y. Hiramatsu, K. Suzuki, T. Nishida, N. Onoda, et al. (mBio 13:e01397-21, 2022, https://doi.org/10.1128/mbio.03197-21) used a mouse model and cellular studies to investigate bacterial and host factors that contribute to cough production during Bordetella pertussis infection. In elegant studies, they found that the bacterial factors pertussis toxin, lipooligosaccharide, and Vag8 function cooperatively to produce cough. These factors induce production of host bradykinin, a known cough inducer that sensitizes the ion channel TRPV1 on neurons, and they investigated host signaling pathways altered by the bacterial factors that exacerbate cough responses. This is a highly significant and important finding that not only elucidates mechanisms underlying the pathophysiology of the severe cough, but also may reveal potential novel therapeutic approaches to treat individuals suffering from the debilitating effects of cough in pertussis.