Carbon dioxide-sensing in organisms and its implications for human disease

Abstract

The capacity of organisms to sense changes in the levels of internal and external gases and to respond accordingly is central to a range of physiologic and pathophysiologic processes. Carbon dioxide, a primary product of oxidative metabolism is one such gas that can be sensed by both prokaryotic and eukaryotic cells and in response to altered levels, elicit the activation of multiple adaptive pathways. The outcomes of activating CO2-sensitive pathways in various species include increased virulence of fungal and bacterial pathogens, prey-seeking behavior in insects as well as taste perception, lung function, and the control of immunity in mammals. In this review, we discuss what is known about the mechanisms underpinning CO2 sensing across a range of species and consider the implications of this for physiology, disease progression, and the possibility of developing new therapeutics for inflammatory and infectious disease.

Fig. 1

Schematic summarizing some of the key outcomes for CO₂ sensing across species (outer circle) and examples of the mechanisms underpinning these effects (inner circle). AC adenylyl cyclase, CA carbonic anhydrase, GC guanylate cyclase, gca growth controlled by abscisic acid, NECs neuroepithelial cells, miR microRNA, NF-kappaB nuclear factor kappa B

Fig. 2

Key outcomes of CO₂ signaling with respect to inflammation, infection, and microbial virulence. Elevated CO₂ leads to suppression of host immunity and enhances microbial adaptation leading to a state where an increased risk of infection is favored by environmental conditions