Maturation signatures of conventional dendritic cell subtypes in COVID-19 reflect direct viral sensing

Marongiu, Laura; Protti, Giulia; Fa, Facchini; Valache, Mihai; Mingozzi, Francesca; Ranzani,; Putignano, Anna Rita; Salviati, Lorenzo; Bevilacqua, Valeria; Curti, Serena Maria; Crosti, Mariacristina; D’Angiò, Mariella; Lr, Bettini; Biondi, Andrea; Nespoli, Luca; Tamini, Nicolò; Mancini, Nicasio; Clementi, Nicola; Abrignani, Sergio; Spreafico, Roberto; Granucci, Francesca

doi:10.1101/2021.03.03.433597

Cited by 4 publications

(3 citation statements)

References 40 publications

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“…The former serve as potent antigen- presenting cells (APCs), while the latter is a specialized subset that can produce type 1 IFN ( 60 , 61 ). It has been found that pDC along with viral sensing, interferon signaling and antigen presentation are more defective in severe versus mild COVID-19 ( 62 – 68 ). Further impairment in DC maturation and function in severe vs. mild disease may be associated with a worse disease ( 69 ).…”

Section: The Relationship Between the Innate Immune System And The Pr...mentioning

confidence: 99%

Immune responses in mildly versus critically ill COVID-19 patients

et al. 2023

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The current coronavirus pandemic (COVID-19), caused by SARS-CoV-2, has had devastating effects on the global health and economic system. The cellular and molecular mediators of both the innate and adaptive immune systems are critical in controlling SARS-CoV-2 infections. However, dysregulated inflammatory responses and imbalanced adaptive immunity may contribute to tissue destruction and pathogenesis of the disease. Important mechanisms in severe forms of COVID-19 include overproduction of inflammatory cytokines, impairment of type I IFN response, overactivation of neutrophils and macrophages, decreased frequencies of DC cells, NK cells and ILCs, complement activation, lymphopenia, Th1 and Treg hypoactivation, Th2 and Th17 hyperactivation, as well as decreased clonal diversity and dysregulated B lymphocyte function. Given the relationship between disease severity and an imbalanced immune system, scientists have been led to manipulate the immune system as a therapeutic approach. For example, anti-cytokine, cell, and IVIG therapies have received attention in the treatment of severe COVID-19. In this review, the role of immunity in the development and progression of COVID-19 is discussed, focusing on molecular and cellular aspects of the immune system in mild vs. severe forms of the disease. Moreover, some immune- based therapeutic approaches to COVID-19 are being investigated. Understanding key processes involved in the disease progression is critical in developing therapeutic agents and optimizing related strategies.

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Section: The Relationship Between the Innate Immune System And The Pr...mentioning

confidence: 99%

Immune responses in mildly versus critically ill COVID-19 patients

et al. 2023

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“…Severe COVID-19 is characterized by increased cell death: the elevated levels of interferon (IFN)-γ and TNF that are observed in patients with severe disease induce a form of cell death called PANoptosis [ 23 ], which initiates a feed-back loop that sustains lymphopenia, tissue damage, and inflammation. Another key feature of the immunosuppressive phase of sepsis is decreased antigen presentation – this is also a hallmark of severe COVID-19, that is characterized by HLA-DR lo circulating monocytes and dendritic cells [ 24 , 25 , 26 ]. In addition, the gene signatures of monocytes derived from patients with severe sepsis and from those with severe COVID-19 are strikingly similar [ 15 ].…”

Section: Covid-19 Is An Inflammatory Disordermentioning

confidence: 99%

Interfering with SARS-CoV-2: are interferons friends or foes in COVID-19?

Zanoni

2021

Current Opinion in Virology

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“…Dendritic cells as professional antigen-presenting cells (APCs) are central players in the initiation of adaptive responses, leading to elimination of viral infections [52] . Analysis of conventional dendritic cells (cDCs) in severe and mild COVID-19 patients illustrated decreased expression of co-stimulatory proteins, MHCII, and TAP molecules and increased levels of pro-inflammatory molecules including complement and coagulation factors in severely ill patients [53] . Moreover, plasmacytoid dendritic cells (pDCs) are known as IFN producers in the innate immune system.…”

Section: Immunoediting In Sars-cov-2mentioning

confidence: 99%

Immunoediting in SARS-CoV-2: Mutual relationship between the virus and the host

Kheshtchin

Bakhshi

Arab

et al. 2022

International Immunopharmacology

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Immunoediting is a well-known concept that occurs in cancer through three steps of elimination, equilibrium, and escape (3Es), where the immune system first suppresses the growth of tumor cells and then promotes them towards the malignancy. This phenomenon has been conceptualized in some chronic viral infections such as HTLV-1 and HIV by obtaining the resistance to elimination and making a persistent form of infected cells especially in untreated patients. Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a heterogeneous disease characterizing from mild/asymptomatic to severe/critical courses with some behavioral aspects in an immunoediting setting. In this context, a coordinated effort between of innate and adaptive immune system leads to detection and destruction of early infection followed by equilibrium between virus-specific responses and infected cells, which eventually end up with an uncontrolled inflammatory response in severe/critical patients. Although the SARS-CoV-2 applies several escape strategies such as mutations in viral epitopes, modulating the interferon response and inhibiting the MHC I molecules similar to the cancer cells, the 3Es hallmark may not occur in all clinical conditions. Here, we discuss how the lesson learnt from cancer immunoediting and accurate understanding of these pathophysiological mechanisms helps to develop more effective therapeutic strategies for COVID-19.

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Maturation signatures of conventional dendritic cell subtypes in COVID-19 reflect direct viral sensing

Cited by 4 publications

References 40 publications

Immune responses in mildly versus critically ill COVID-19 patients

Immune responses in mildly versus critically ill COVID-19 patients

Interfering with SARS-CoV-2: are interferons friends or foes in COVID-19?

Immunoediting in SARS-CoV-2: Mutual relationship between the virus and the host

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