Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 2 de 2
Filter
1.
Emerg Microbes Infect ; 11(1): 406-411, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1595567

ABSTRACT

Patients with recent pandemic coronavirus disease 19 (COVID-19) complain of neurological abnormalities in sensory functions such as smell and taste in the early stages of infection. Determining the cellular and molecular mechanism of sensory impairment is critical to understand the pathogenesis of clinical manifestations, as well as in setting therapeutic targets for sequelae and recurrence. The absence of studies utilizing proper models of human peripheral nerve hampers an understanding of COVID-19 pathogenesis. Here, we report that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) directly infects human peripheral sensory neurons, leading to molecular pathogenesis for chemosensory impairments. An in vitro system utilizing human embryonic stem cell (hESC)-derived peripheral neurons was used to model the cellular and molecular pathologies responsible for symptoms that most COVID-19 patients experience early in infection or may develop as sequelae. Peripheral neurons differentiated from hESCs expressed viral entry factor ACE2, and were directly infected with SARS-CoV-2 via ACE2. Human peripheral neurons infected with SARS-CoV-2 exhibited impaired molecular features of chemosensory function associated with abnormalities in sensory neurons of the olfactory or gustatory organs. Our results provide new insights into the pathogenesis of chemosensory dysfunction in patients with COVID-19.


Subject(s)
COVID-19/complications , Olfaction Disorders/etiology , SARS-CoV-2 , Sensory Receptor Cells/virology , Taste Disorders/etiology , Angiotensin-Converting Enzyme 2/physiology , Humans
2.
Front Immunol ; 12: 785355, 2021.
Article in English | MEDLINE | ID: covidwho-1594099

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.


Subject(s)
Aging/immunology , COVID-19/immunology , Immunity, Innate/immunology , Lung/immunology , Nociceptors/immunology , SARS-CoV-2/immunology , Transient Receptor Potential Channels/immunology , Aged , COVID-19/virology , Humans , Lung/innervation , Lung/virology , Nociceptors/metabolism , Nociceptors/virology , SARS-CoV-2/physiology , Sensory Receptor Cells/immunology , Sensory Receptor Cells/metabolism , Sensory Receptor Cells/virology , Transient Receptor Potential Channels/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL