Type I IFN-dependent antibody response at the basis of sex dimorphism in the outcome of COVID-19

Gabriele, Lucia; Fragale, Alessandra; Romagnoli, Giulia; Parlato, Stefania; Lapenta, Caterina; Santini, Stefano M.; Ozato, Keiko; Capone, Imerio

doi:10.1016/j.cytogfr.2020.10.001

Cited by 18 publications

(19 citation statements)

References 92 publications

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“…This idea is also supported by a recent report showing that loss-of-function mutation of X-chromosomal TLR7 is associated with impaired type I IFN responses of young male patients with severe COVID-19 that further emphasizes the importance of intact TLR7-mediated type I IFN responses in the pathogenesis of the disease [289]. Moreover, pDC-derived type I IFNs mediate B cell activation and differentiation into plasma cells, thus are essential to elicit an optimal antibody response to viral infection including SARS-CoV-2 infection as well [290].…”

Section: Discussionmentioning

confidence: 99%

Type I Interferon Production of Plasmacytoid Dendritic Cells under Control

Bencze

Fekete

Pázmándi

2021

IJMS

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One of the most powerful and multifaceted cytokines produced by immune cells are type I interferons (IFNs), the basal secretion of which contributes to the maintenance of immune homeostasis, while their activation-induced production is essential to effective immune responses. Although, each cell is capable of producing type I IFNs, plasmacytoid dendritic cells (pDCs) possess a unique ability to rapidly produce large amounts of them. Importantly, type I IFNs have a prominent role in the pathomechanism of various pDC-associated diseases. Deficiency in type I IFN production increases the risk of more severe viral infections and the development of certain allergic reactions, and supports tumor resistance; nevertheless, its overproduction promotes autoimmune reactions. Therefore, the tight regulation of type I IFN responses of pDCs is essential to maintain an adequate level of immune response without causing adverse effects. Here, our goal was to summarize those endogenous factors that can influence the type I IFN responses of pDCs, and thus might serve as possible therapeutic targets in pDC-associated diseases. Furthermore, we briefly discuss the current therapeutic approaches targeting the pDC-type I IFN axis in viral infections, cancer, autoimmunity, and allergy, together with their limitations defined by the Janus-faced nature of pDC-derived type I IFNs.

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Section: Discussionmentioning

confidence: 99%

Type I Interferon Production of Plasmacytoid Dendritic Cells under Control

Bencze

Fekete

Pázmándi

2021

IJMS

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“…Of note, IFN-α production following TLR7 stimulation is greater in pDC from females than from males. It has been hypothesized that type I IFN production by pDC may control early SARS-CoV-2 infection in females better than in males, leading to better outcomes on average and explaining why 70% of those who die from the disease are male [ 59 ].…”

Section: DC and Innate Immunity To Covid-19mentioning

confidence: 99%

A Missing Link: Engagements of Dendritic Cells in the Pathogenesis of SARS-CoV-2 Infections

Fisk

Upreti

Kung

2021

IJMS

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Dendritic cells (DC) connect the innate and adaptive arms of the immune system and carry out numerous roles that are significant in the context of viral disease. Their functions include the control of inflammatory responses, the promotion of tolerance, cross-presentation, immune cell recruitment and the production of antiviral cytokines. Based primarily on the available literature that characterizes the behaviour of many DC subsets during Severe acute respiratory syndrome (SARS) and coronavirus disease 2019 (COVID-19), we speculated possible mechanisms through which DC could contribute to COVID-19 immune responses, such as dissemination of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to lymph nodes, mounting dysfunctional inteferon responses and T cell immunity in patients. We highlighted gaps of knowledge in our understanding of DC in COVID-19 pathogenesis and discussed current pre-clinical development of therapies for COVID-19.

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“…For the most appropriate viral response, DCs instruct T cells toward anti-viral Th1 via the production of instructive innate cytokines, such as IFN-β and IL-12, which leads to the production of IFN-γ and proper viral clearance [ 45 ]. However, many respiratory viral infections, such as RSV, RV, and SARS-CoV-2, have the ability to dampen type-1 immunity through multiple mechanisms [ 46 , 47 , 48 , 49 , 50 , 51 ] that lead to a decrease in T cell production of important anti-viral cytokines, such as IL-2 and IFN-γ. These skewed responses lead to an imbalanced immune response away from Th1 anti-viral immunity toward a predominantly Th2/Th17 pathogenic response accompanied by a diminished CD8+ cytotoxic T cell response.…”

Section: Overview Of Immune Response To Respiratory Virusesmentioning

confidence: 99%

“…Perhaps these trained immune responses to early-life vaccines may contribute to the protection observed in children during SARS-CoV-2 infections that wanes as we age. On the other hand, studies have linked inappropriate DC-specific trained immunity that leads to a decrease in type-1 IFN levels as a possible route for enhanced COVID-19 disease in susceptible populations [ 49 ]. These observations, along with other studies that have shown that DCs from naturally infected individuals have decreased sensitivity to future unrelated TLR signaling [ 65 , 66 ], suggest that proper activation of DCs and appropriate TLR targeting (i.e., to enhance Th1 immunity) during vaccination may lead to “training” of innate responses to future encounters with unrelated pathogens.…”

Section: Overview Of Immune Response To Respiratory Virusesmentioning

confidence: 99%

“…In another study, intranasal administration of a poly(I:C)-adjuvanted vaccine induced IFN-β and IFN-γ production and protected animals from respiratory viral infections caused by influenza and SARS-CoV [ 93 ]. Studies have identified the TLR7 pathway as more activated in females compared to males following SARS-CoV-2 infection and linked to protection from severe disease [ 49 ], suggesting that viral stimulation through TLR7 may lead to a stronger type-1 IFN response in females and that adjuvant targeting of this pathway may be beneficial, especially in males. Mice immunized with inactivated SARS-CoV and the TLR9 ligand, CpG, also showed promising results [ 94 ].…”

Section: Novel Vaccination Approaches Against Respiratory Viral Inmentioning

confidence: 99%

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Harnessing Cellular Immunity for Vaccination against Respiratory Viruses

Lukacs

Malinczak

2020

Vaccines

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Severe respiratory viral infections, such as influenza, metapneumovirus (HMPV), respiratory syncytial virus (RSV), rhinovirus (RV), and coronaviruses, including severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), cause significant mortality and morbidity worldwide. These viruses have been identified as important causative agents of acute respiratory disease in infants, the elderly, and immunocompromised individuals. Clinical signs of infection range from mild upper respiratory illness to more serious lower respiratory illness, including bronchiolitis and pneumonia. Additionally, these illnesses can have long-lasting impact on patient health well beyond resolution of the viral infection. Aside from influenza, there are currently no licensed vaccines against these viruses. However, several research groups have tested various vaccine candidates, including those that utilize attenuated virus, virus-like particles (VLPs), protein subunits, and nanoparticles, as well as recent RNA vaccines, with several of these approaches showing promise. Historically, vaccine candidates have advanced, dependent upon the ability to activate the humoral immune response, specifically leading to strong B cell responses and neutralizing antibody production. More recently, it has been recognized that the cellular immune response is also critical in proper resolution of viral infection and protection against detrimental immunopathology associated with severe disease and therefore, must also be considered when analyzing the efficacy and safety of vaccine candidates. These candidates would ideally result in robust CD4+ and CD8+ T cell responses as well as high-affinity neutralizing antibody. This review will aim to summarize established and new approaches that are being examined to harness the cellular immune response during respiratory viral vaccination.

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Type I IFN-dependent antibody response at the basis of sex dimorphism in the outcome of COVID-19

Cited by 18 publications

References 92 publications

Type I Interferon Production of Plasmacytoid Dendritic Cells under Control

Type I Interferon Production of Plasmacytoid Dendritic Cells under Control

A Missing Link: Engagements of Dendritic Cells in the Pathogenesis of SARS-CoV-2 Infections

Harnessing Cellular Immunity for Vaccination against Respiratory Viruses

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