Innate Receptors Expression by Lung Nociceptors: Impact on COVID-19 and Aging

Abstract

The lungs are constantly exposed to non-sterile air which carries harmful threats, such as particles and pathogens. Nonetheless, this organ is equipped with fast and efficient mechanisms to eliminate these threats from the airways as well as prevent pathogen invasion. The respiratory tract is densely innervated by sensory neurons, also known as nociceptors, which are responsible for the detection of external stimuli and initiation of physiological and immunological responses. Furthermore, expression of functional innate receptors by nociceptors have been reported; however, the influence of these receptors to the lung function and local immune response is poorly described. The COVID-19 pandemic has shown the importance of coordinated and competent pulmonary immunity for the prevention of pathogen spread as well as prevention of excessive tissue injury. New findings suggest that lung nociceptors can be a target of SARS-CoV-2 infection; what remains unclear is whether innate receptor trigger sensory neuron activation during SARS-CoV-2 infection and what is the relevance for the outcomes. Moreover, elderly individuals often present with respiratory, neurological and immunological dysfunction. Whether aging in the context of sensory nerve function and innate receptors contributes to the disorders of these systems is currently unknown. Here we discuss the expression of innate receptors by nociceptors, particularly in the lungs, and the possible impact of their activation on pulmonary immunity. We then demonstrate recent evidence that suggests lung sensory neurons as reservoirs for SARS-CoV-2 and possible viral recognition via innate receptors. Lastly, we explore the mechanisms by which lung nociceptors might contribute to disturbance in respiratory and immunological responses during the aging process.

The Emerging Role of Photobiomodulation in COVID-19 Therapy Part II

“…As COVID-19 exhibits significant involvement of the central and peripheral nervous system and the brain 188,189,190,132 , a number of different protocols are required to treat nerve dysfunction along the spinal cord 171,175,191 , cranial nerves of the autonomous nervous system (ANS), and spinal nerves of the peripheral nervous system (PNS) 192,193,194,195,196,197 . PBM may be performed locally targeting COVID impaired sensory nerve receptors 198,199,200,201,202 , over-active nociceptors 203,204,205 , ganglions 206 , or to manage pain transduction along the spinal cord and peripheral nerves 207,208 .…”

SARS-Cov2 acute and post-active infection in the context of autoimmune and chronic inflammatory diseases

“…As reported with tobacco smoking and air pollutants, COVID-19 can act on cells in mucosal sites (mouth, lung and gut) to promote the induction of PADI-4 and in turn to the formation of citrullinated histones [ 129 , 130 ]. This process is suspected of becoming chronic in PACS since lung sensory neurons and the gut represent mucosal reservoirs for SARS-Cov2 [ 26 , 131 , 132 ]. Moreover, COVID-19 infection is primarily a respiratory infection with 70–80% of patients presenting radiographic lung involvement that appear simultaneously with fever, in some cases, even precedes fever [ 133 , 134 ].…”