Single-cell transcriptional landscape of circulating Tfh and Treg cells in COVID-19 patients

• Autor(a) principal: Fonseca, Diogo Martins
• Data de Publicação: 2023
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10362/160963
• topic: Viral Infection; Immune response; Tfh cells; Treg cells; Single-cell RNA-Seq.; Domínio/Área Científica::Engenharia e Tecnologia::Outras Engenharias e Tecnologias

The emergence of COVID-19 has posed an unprecedented challenge to global healthcare systems and socioeconomic progress. Understanding the immune response against SARS- CoV-2 is crucial for developing effective therapeutic and prophylactic strategies and enhanc- ing preparedness for future airborne virus threats. A key aspect of this response is the regula- tion of antibody production, which not only drives protective immunity following infection but also plays a pivotal role in vaccine efficacy. Equally important is comprehending the im- munosuppressive mechanisms in severely ill patients to prevent excessive immune responses, mitigate immunopathology, and promote controlled antiviral immunity. Tfh cells are essential for guiding B cells to generate high-affinity neutralizing antibodies, while Treg cells act as immune suppressors to prevent immune overactivity. In our study, we employed advanced computational methods, including single-cell transcriptomics analysis, to unravel the intricate dynamics of both Tfh and Treg populations elicited in response to SARS-CoV-2 infection. We conducted single-cell resolution analyses of circulating Tfh cells (cTfh) and Treg cells in se- verely ill COVID-19 patients. For this, we sorted Tfh and Treg cells from peripheral blood samples and performed single-cell RNA sequencing. In COVID-19 patients, cTfh cell clusters exhibited segregation based on two critical factors: activation status and cTfh subtype, a phe- nomenon not observed in cTfh cells from healthy donors. Furthermore, our investigation into Treg cell heterogeneity in both healthy and COVID-19 conditions unveiled distinct cell popu- lations varying in activation states and Th signatures. In conclusion, our research offers a com- prehensive resource on the transcriptomics of various Tfh and Treg populations and their re- sponses to viral infections.