BACKGROUND: Morbidity and mortality from COVID-19 caused by novel coronavirus SARS-CoV-2 is accelerating worldwide, and novel clinical presentations of COVID-19 are often reported. The range of human cells and tissues targeted by SARS-CoV-2, its potential receptors and associated regulating factors are still largely unknown. The aim of our study was to analyze the expression of known and potential SARS-CoV-2 receptors and related molecules in the extensive collection of primary human cells and tissues from healthy subjects of different age and from patients with risk factors and known comorbidities of COVID-19. METHODS: We performed RNA sequencing and explored available RNA-Seq databases to study gene expression and co-expression of ACE2, CD147 (BSG), and CD26 (DPP4) and their direct and indirect molecular partners in primary human bronchial epithelial cells, bronchial and skin biopsies, bronchoalveolar lavage fluid, whole blood, peripheral blood mononuclear cells (PBMCs), monocytes, neutrophils, DCs, NK cells, ILC1, ILC2, ILC3, CD4+ and CD8+ T cells, B cells, and plasmablasts. We analyzed the material from healthy children and adults, and from adults in relation to their disease or COVID-19 risk factor status. RESULTS: ACE2 and TMPRSS2 were coexpressed at the epithelial sites of the lung and skin, whereas CD147 (BSG), cyclophilins (PPIA andPPIB), CD26 (DPP4), and related molecules were expressed in both epithelium and in immune cells. We also observed a distinct age-related expression profile of these genes in the PBMCs and T cells from healthy children and adults. Asthma, COPD, hypertension, smoking, obesity, and male gender status generally led to the higher expression of ACE2- and CD147-related genes in the bronchial biopsy, BAL, or blood. Additionally, CD147-related genes correlated positively with age and BMI. Interestingly, we also observed higher expression of CD147-related genes in the lesional skin of patients with atopic dermatitis. CONCLUSIONS: Our data suggest different receptor repertoire potentially involved in the SARS-CoV-2 infection at the epithelial barriers and in the immune cells. Altered expression of these receptors related to age, gender, obesity and smoking, as well as with the disease status, might contribute to COVID-19 morbidity and severity patterns.
- Klíčová slova
- COPD, COVID-19, COVID-19 children, SARS receptor, asthma, hypertension, obesity,
- MeSH
- angiotensin-konvertující enzym 2 genetika imunologie MeSH
- basigin genetika imunologie MeSH
- bronchiální astma epidemiologie genetika imunologie MeSH
- chronická nemoc epidemiologie MeSH
- chronická obstrukční plicní nemoc epidemiologie genetika imunologie MeSH
- COVID-19 epidemiologie genetika imunologie MeSH
- dipeptidylpeptidasa 4 genetika imunologie MeSH
- dítě MeSH
- dospělí MeSH
- exprese genu genetika MeSH
- hypertenze epidemiologie genetika imunologie MeSH
- kojenec MeSH
- komorbidita MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- obezita epidemiologie genetika imunologie MeSH
- předškolní dítě MeSH
- přirozená imunita imunologie MeSH
- rizikové faktory MeSH
- SARS-CoV-2 genetika imunologie MeSH
- senioři MeSH
- věkové faktory MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- ACE2 protein, human MeSH Prohlížeč
- angiotensin-konvertující enzym 2 MeSH
- basigin MeSH
- BSG protein, human MeSH Prohlížeč
- dipeptidylpeptidasa 4 MeSH
- DPP4 protein, human MeSH Prohlížeč
The acquisition of the infant gut microbiota is key to establishing a host-microbiota symbiosis. Microbially produced metabolites tightly interact with the immune system, and the fermentation-derived short-chain fatty acid butyrate is considered an important mediator linked to chronic diseases later in life. The intestinal butyrate-forming bacterial population is taxonomically and functionally diverse and includes endospore formers with high transmission potential. Succession, and contribution of butyrate-producing taxa during infant gut microbiota development have been little investigated. We determined the abundance of major butyrate-forming groups and fermentation metabolites in faeces, isolated, cultivated and characterized the heat-resistant cell population, which included endospores, and compared butyrate formation efficiency of representative taxa in batch cultures. The endospore community contributed about 0.001% to total cells, and was mainly composed of the pioneer butyrate-producing Clostridium sensu stricto. We observed an increase in abundance of Faecalibacterium prausnitzii, butyrate-producing Lachnospiraceae and faecal butyrate levels with age that is likely explained by higher butyrate production capacity of contributing taxa compared with Clostridium sensu stricto. Our data suggest that a successional arrangement and an overall increase in abundance of butyrate forming populations occur during the first year of life, which is associated with an increase of intestinal butyrate formation capacity.
- MeSH
- Bacteria klasifikace genetika izolace a purifikace metabolismus MeSH
- butyráty metabolismus MeSH
- feces chemie mikrobiologie MeSH
- fermentace MeSH
- kojenec MeSH
- kyseliny mastné těkavé metabolismus MeSH
- lidé MeSH
- spory bakteriální klasifikace genetika izolace a purifikace metabolismus MeSH
- střeva růst a vývoj mikrobiologie MeSH
- střevní mikroflóra fyziologie MeSH
- Check Tag
- kojenec MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- butyráty MeSH
- kyseliny mastné těkavé MeSH