key: cord-0752404-5cpwqxxs
authors: Galati, Domenico; Zanotta, Serena; Capitelli, Ludovica; Bocchino, Marialuisa
title: A bird's eye view on the role of dendritic cells in SARS‐CoV‐2 infection: Perspectives for immune‐based vaccines
date: 2021-07-24
journal: Allergy
DOI: 10.1111/all.15004
sha: 5c117113750b453b86906555485a12a68d03c2ac
doc_id: 752404
cord_uid: 5cpwqxxs

Coronavirus disease‐19 (COVID‐19) is a complex disorder caused by the pandemic diffusion of a novel coronavirus named SARS‐CoV‐2. Clinical manifestations vary from silent infection to severe pneumonia, disseminated thrombosis, multi‐organ failure, and death. COVID‐19 pathogenesis is still not fully elucidated, while increasing evidence suggests that disease phenotypes are strongly related to the virus‐induced immune system's dysregulation. Indeed, when the virus‐host cross talk is out of control, the occurrence of an aberrant systemic inflammatory reaction, named “cytokine storm,” leads to a detrimental impairment of the adaptive immune response. Dendritic cells (DCs) are the most potent antigen‐presenting cells able to support innate immune and promote adaptive responses. Besides, DCs play a key role in the anti‐viral defense. The aim of this review is to focus on DC involvement in SARS‐CoV‐2 infection to better understand pathogenesis and clinical behavior of COVID‐19 and explore potential implications for immune‐based therapy strategies.

At the end of 2019, several human cases of infection by a novel coronavirus named SARS-CoV-2 were related to the Huanan Seafood Wholesale Market, Wuhan, China. Since then, the wide dissemination of the infection and of its related disease, called COVID-19, to every continent is forcing us to live with this virus for a probably very long time. COVID-19 is a complex disorder, with the lung being the most frequently affected site. Manifestations of COVID-19 range from mild upper respiratory illness to severe bilateral pneumonia, acute respiratory distress syndrome (ARDS), disseminated thrombosis, multi-organ failure, and death. [1] [2] [3] However, not all infected individuals develop a clinically significant disease. Early identification of healthy virus carriers has been the cornerstone of campaigns to prevent infection spread since Germany's first report which demonstrated their potential contagiousness. 4 SARS-CoV-2 is a lipid-enveloped positive-sense RNA virus that uses a heavily glycosylated spike (S) protein to attach to the cell membrane and penetrate the host cell. [5] [6] [7] The S protein consists of two functional subunits: S1 contains the receptor-binding domain that allows the engagement of the angiotensin-converting enzyme (ACE)-2 on the target cell surface, while S2 is involved in the viruscell fusion process. 7, 8 As ACE-2 is highly expressed in trachea and bronchial epithelia, 9 in type II alveolar cells, 10 and in nasal epithelial cells, 11 these locations have a key role in the initial viral infection and spread. Nevertheless, ACE-2 expression in additional tissue/ organ-specific cells makes them at potentially high risk for infection. 12 Likewise, infection by SARS-CoV-2 can occur regardless of ACE-2 expression, 13 through alternative receptors including C-type lectin receptors (CLR), toll-like receptors (TLR), neuropilin (NRP)-1, dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN), homolog dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin related (L-SIGN), and macrophage galactose-type lectin (MGL). 13, 14 Pathogenesis of COVID-19 is a puzzle not fully elucidated. [15] [16] [17] [18] However, based on clinical and experimental data, there is growing evidence that disease phenotypes are strongly related to the degree of the immune system's dysregulation in response to the virus, as depicted in detail in the review by Sokolowska et al 19 Briefly, innate immune cells act as the first line of defense through the recognition of pathogen-associated molecular patterns (PAMPs), which allow the activation 20,21 of signaling pathways leading to the expression of anti-viral molecules, including interferons (IFNs), interferonstimulated genes (ISGs), and inflammatory chemokines and cytokines. 20, 22 However, when the virus-immune system cross talk is out of control, a detrimental systemic inflammatory reaction, named "cytokine storm," can occur in infected individuals along with a simultaneous impairment of the adaptive immune response. 15, 20, 23 Unfortunately, this scenario is not an infrequent occurrence in the COVID-19 patient and is burdened by devastating effects because the host cannot efficiently counter the virus while harming itself. 24, 25 In line with these considerations, a first Chinese report showed that 99 subjects investigated in Wuhan had increased total neutrophils (38%), reduced total lymphocytes (35%), increased serum levels of interleukin (IL)-6 (52%), and increased c-reactive protein (CRP) (84%). 25, 26 Also, high amounts of IL-1β, interferon (IFN)γ, IFN induced protein-10 (IP-10), and monocyte chemoattractant protein (MCP)-1 were observed in infected patients, resulting in activated T-helper (Th)-1 immune responses. Interestingly, higher levels of IL-6, granulocyte-colony stimulating factor (G-CSF), IP-10, MCP-1, macrophage inflammatory protein (MIP)-1α, and tumor necrosis factor (TNF)α were associated with disease severity. 25, 26 A retrospective study performed in 452 SARS-CoV-2-infected patients has demonstrated that depletion of CD4 + T cells was more prominent in advanced disease. Conversely, there were no significant changes in the number of CD8 + T cells and B lymphocytes. 27 An additional report on 140 COVID-19 patients further suggested low blood counts of eosinophils and lymphocytes as potential markers for diagnosis purposes. 19, 28 However, the pathophysiological mechanism of these observations merits further study. In particular, when looking at lymphopenia (i.e., apoptosis, virus-mediated cytopathic effect) it seems that it occurs along with functional T-cell defects. 19 There is evidence that T-helper 17 cells actively participate to the cytokine storm response, 29 while T regulatory cells are decreased. 30 Also, highly activated lymphocytes exhibit an exhausted phenotype with high PD-1 expression, which decreases with virus clearance along with cell function restoration. 31 Finally, a further explanation of impairment of T-cell functionality and anti-viral activities may rely on a defective cell priming upon specific antigen (Ag) presentation. In this issue, regulation of the immune response through the conversion of type-1 to type-2, activation of M2 macrophages, and maturation of dendritic cells (DCs) by mesenchymal stem cells has been proposed as an alternative therapeutic strategy in COVID- 19. 32 Notably, DCs and macrophages are the main components of the mononuclear phagocytic system. In particular, DCs are the most specialized and potent Ag-presenting cells (APCs) of the immune system. They promote the activation of naive and memory T cells, thus polarizing the immune response. Broadly studied in different experimental and internal medicine areas, including transplantation, allergy, autoimmunity, infectious diseases, and cancer, [33] [34] [35] [36] DCs also play a crucial role in the host defense against viruses and exert tolerogenic activities. 37 Given the multiple and pleiotropic properties of DCs and their "bridge" position between innate and adaptive immunity, the purpose of this review is to put together the available data concerning the involvement of these cells in SARS-CoV-2 infection. This effort aims to better understand the pathogenesis of COVID-19 and make considerations on the potential use of DCs in immune-based treatments to counter it.

DCs encompass a heterogeneous family of bone marrow-derived cells and are found in peripheral blood, lymphoid organs, and tissues. According to the last DC classification, conventional DCs (cDCs) and plasmacytoid DCs (pDCs) are the two main functional DC subtypes. 38, 39 Circulating DCs include CD11C + cDCs, that are cDC2 CD1C + and cDC1 CD141 + cells, and CD11C − pDCs, that are CD123 + and CD303 + cells. 38, 39 Conventional DCs play a fundamental role in the Ag processing and presentation to lymphocytes. On the other, pDCs display high anti-viral activities due to their ability to produce type I interferon (IFN) and are thought to be involved in immune tolerance. 40 and endowed with a strong potential to regulate tumor immunity. [43] [44] [45] [46] In reality, human DC subsets are quite heterogeneous with still little agreement on the identification and naming of new subtypes.

This makes their classification a dynamic process with the need for continuous updating. About that, the finer characterization of at least two subtypes of cDCs2 (A and B) seems to have gained consensus more recently. Conventional DCs2-A express higher levels of CD11c, CD1c, and major histocompatibility complex (MHC) class II genes along with CD32 + and CD5. Previously named CD3, cDCs2-B are CD14 + /CD36 + /CD163 + and express low levels of CD5 (CD5 low ) and high amounts of inflammatory cytokines. 39, 47, 48 High-dimensional cytometry has permitted to redraw the blood cDC2 phenotype in CD1c + BTLA + with low (cDC2-B) to high expression of CD5 (previously cDC2-A), and DC3 phenotype in CD88 − CD1c + CD163 + with low to high expression of CD14, improving functional description of DC3 as a lineage of inflammatory DCs holding a strong potentiality to regulate anti-tumor cytotoxic T-cell immune responses. 43, 45, 46 Additionally, single-cell RNAseq studies have identified a further subtype of CD16 + /CD141 − /CD1c − DCs that cluster separately from monocytes. 42 The expression of a broad range of toll-like receptors (TLR) and inflammatory cytokines upon lipopolysaccharide/IFNγ stimulation makes these cells as ideal immune sentinels for detecting invading pathogens. 49 Finally, the existence in the human system of non-canonical DC subtypes with merged characteristics of cDCs and pDCs has also been proposed. This is the case of blood CD123 + cells expressing the distinctive markers AXL and SIGLEC6. 42, 50 While their identity is still unclear, AXL + SIGLEC6 + CD123 low CD11c high DCs look closely related to cDCs2. By the other, AXL + SIGLEC6 + CD123 high CD11c low DCs are phenotypically similar to pDCs but functionally assimilable to cDCs2. 42, 45, 50 With reference to tissue-resident DCs, they are subdivided into lymphoid and non-lymphoid. Lymphoid-resident DCs are usually found in the thymus, spleen, and lymph nodes and consist of phenotypically different subtypes able to process and present antigens entering these sites. 51 Specific tissue localization discriminates non- Phenotypic profiles and functional pathways are different in naïve (immature) and mature DCs. Immature DCs display low levels of MHC and co-stimulatory molecules. They are mainly located in barrier tissues, such as the skin, the mucosal surfaces, and lymphoid organs, where they act as sentinels committed to Ag uptake and processing. Tissue damage, inflammatory processes, microorganisms, and tumor-derived products may promote the maturation of DCs.

After that, DCs lose their endocytic activity and acquire the ability to produce a wide array of immune-stimulating cytokines, such as IL-12 and type I IFN, which in turn regulate the activity of effector innate immune cells. Moreover, mature DCs possess an increased migratory potential to lymph nodes and lymphoid organs and upregulate the expression of CD80-CD86 co-stimulatory molecules to drive adaptive immune responses through an efficient Ag presentation to CD4 and CD8 T lymphocytes. 53,54

A large number of studies have amply demonstrated the crucial role that DCs play in infectious diseases. Accordingly, these cells are highly likely to also contribute to the pathogenesis of SARS-CoV-2 infection. [55] [56] [57] As previously mentioned, ACE-2 is an essential receptor for SARS-CoV-2 entry into host cells through the interaction with the spike protein. ACE-2 expression by interstitial lung DCs suggests that these cells can be infected by SARS-CoV-2. 8 

The subtle interplay between sentinel DCs and SARS-CoV-2 remains elusive, while some similarities are likely with the SARS-CoV infection model. DC maturation was impaired by SARS-CoV, hampering an appropriate activation of anti-viral adaptive immunity through a decreased expression of class I and II MHC and co-stimulatory molecules (CD40 and CD86). 66 Also, SARS-CoV failed to trigger a significant production of anti-viral cytokines such as IFNα, IFNβ, week) reduction of mature CD80 + /CD86 + cDCs and total pDCs has been correlated with disease severity. 84 In conclusion, through a synoptic evaluation of the presented data, it could be speculated that the reduced numbers of DCs and the dysregulated IFN signaling may be involved in the impaired progression from innate to adaptive immunity as evasion strategies adopted by SARS-CoV-2 with significant impact on disease outcomes. It is possible to assume that this scenario may contribute to the failure of the so-called trained immunity to keep viral infection under control and avoid hyper-inflammation, in analogy with other models of infection of DCs. 89, 90 Interestingly, the weakness of this process, which enables "memory" innate immune cells to quickly respond to unrelated recalling stimuli through the epigenetic reprogramming of IFN and immune signaling, has been linked to recognized risk factors for a worst COVID-19 prognosis, including older age, comorbidities, and male gender. 91 With respect to this last issue, epidemiological data have clearly shown sex-based differences in COVID-19 outcome, with men accounting for about 70% of deaths. 92 The sex-based difference in antibody response is a deeply characterized immunological process that may account for this observation as well. Interestingly, it has been hypothesized that X-linked immune genes involved in pDC-mediated type I IFN signaling occur more efficiently in females leading to the efficient production of SARS-CoV-2 neutralizing antibodies. 71 The ability of estrogen to stimulate DCs is an additional protective factor that may help explain why women are affected but less severe forms of COVID-19 with reduced mortality. 93 An overview of the DC involvement in SARS-CoV-2 infection is illustrated in Figure 2 .

The SARS-CoV-2-related pandemic has demonstrated a striking demographic bias in the number of cases and deaths affecting the elderly subjects and especially those with comorbidities with an increased risk for worst prognosis and mortality. Older patients for these characteristics also represent a sensitive target in the case of vaccination against COVID-19 for the greater risk of anaphylactic reactions, as recently reported by Bousquet et al 2, 94 Immune-senescence results from the imbalance between inflammatory and anti-inflammatory mechanisms that lead to chronic inflammation with a significant impact on aged individuals' survival and fragility. Interestingly, immune-senescence is part of the so-called "inflamm-aging," which is characterized by reduced ability to tolerate an inflammatory milieu and increased production of inflammatory cytokines, acute-phase proteins, and oxidative stress. 95, 96 It has been shown that immune-senescence can influ- account for an impairment of Ag presentation in these patients. 102, 103 A comparison study between MIS-C and COVID-19 children has revealed that circulating pDCs were more severely decreased in the former than in the latter. 104 Interestingly, COVID-19 children also showed higher IFNα plasma levels and increased expression of type I IFNs inducible genes than MIS-C patients, clearly strengthening the key role that pDCs have in anti-viral immunity. 69

Current evidence does not suggest a higher risk for severe COVID-19

in allergic subjects. 105 One explanation may rely on the finding that asthma and allergic respiratory disorders have been associated with a significant reduction of ACE-2 expression in nasal and bronchial cells, both in adults and children. 19 It is of interest that some of the most hopeful anti-COVID-19

vaccines use nanocarriers for packaging to improve stability and ensure efficient Ag processing. In particular, NVX-CoV2373, a self-assembled nanoparticle vaccine derived from the recombi- Future efforts should be to analyze in greater detail the interactions between SARS-CoV-2 and DC subsets during the different phases of the natural history of the infection/disease. Indeed, a more comprehensive understanding will help to decipher still unclear aspects of pathogenesis while offering the opportunity to identify sensitive targets for new therapies.

All authors declare that they have no conflict of interest.

All authors contributed to the writing and editing of the review. All authors approved the final version.

Not applicable. This is a review and not an original paper.

Not applicable. This is a review and not an original paper.

https://orcid.org/0000-0001-5613-9149

Clinical features and prognostic factors of patients with COVID-19 in Henan Province

Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72314 cases from the Chinese center for disease control and prevention

The COVID-19 puzzle: deciphering pathophysiology and phenotypes of a new disease entity

Transmission of 2019-nCoV infection from an asymptomatic contact in Germany

Beyond shielding: the roles of glycans in the SARS-CoV-2 spike protein

Can SARS-CoV-2 virus use multiple receptors to enter host cells?

Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein

Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor

Influenza and SARScoronavirus activating proteases TMPRSS2 and HAT are expressed at multiple sites in human respiratory and gastrointestinal tracts

COVID-19: a new virus, but a familiar receptor and cytokine release syndrome

SARS-CoV-2 entry genes are most highly expressed in nasal goblet and ciliated cells within human airways

Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection

SARS-CoV-2 spike protein interacts with multiple innate immune receptors

CD209L/L-SIGN and CD209/ DC-SIGN act as receptors for SARS-CoV-2 and are differentially expressed in lung and kidney epithelial and endothelial cells

SARS-CoV-2: a storm is raging

COVID-19 infection: the perspectives on immune responses

COVID-19: a promising cure for the global panic

Clinical characteristics of coronavirus disease 2019 in China

Immunology of COVID-19: mechanisms, clinical outcome, diagnostics, and perspectives-a report of the European academy of allergy and clinical immunology (EAACI)

The COVID-19 cytokine storm; what we know so far

Pattern recognition receptors and the innate immune response to viral infection

Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology

Disharmonic inflammatory signatures in COVID-19: augmented neutrophils' but impaired monocytes' and dendritic cells' responsiveness

Clinical and immunological features of severe and moderate coronavirus disease 2019

Clinical features of patients infected with 2019 novel coronavirus in Wuhan

Immune responses in COVID-19 and potential vaccines: lessons learned from SARS and MERS epidemic

Dysregulation of immune response in patients with COVID-19 in Wuhan, China

Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan

Pathological findings of COVID-19 associated with acute respiratory distress syndrome

Is global BCG vaccination-induced trained immunity relevant to the progression of SARS-CoV-2 pandemic?

Reduction and functional exhaustion of T cells in patients with coronavirus disease 2019 (COVID-19)

Mesenchymal stromal cells as potential immunomodulatory players in severe acute respiratory distress syndrome induced by SARS-CoV-2 infection

Severe depletion of peripheral blood dendritic cell subsets in obstructive sleep apnea patients: a new link with cancer?

Circulating dendritic cells are severely decreased in idiopathic pulmonary fibrosis with a potential value for prognosis prediction

Circulating dendritic cells deficiencies as a new biomarker in classical Hodgkin lymphoma

Imbalance of circulating dendritic cell subsets in chronic obstructive pulmonary disease

Decisions about dendritic cells: past, present, and future

Nomenclature of monocytes and dendritic cells in blood

Development and function of dendritic cell subsets

Ontogeny and functional specialization of dendritic cells in human and mouse

Dendritic cells as sensors, mediators, and regulators of ischemic injury

Single-cell RNA-seq reveals new types of human blood dendritic cells, monocytes, and progenitors

Single-cell analysis of human mononuclear phagocytes reveals subset-defining markers and identifies circulating inflammatory dendritic cells

Human dendritic cell subsets: an update

Transcriptional and functional analysis of CD1c( + ) human dendritic cells identifies a CD163( + ) subset priming CD8( + )CD103( + ) T cells

Differential IRF8 transcription factor requirement defines two pathways of dendritic cell development in humans

Human blood CD1c + dendritic cells encompass CD5high and CD5low subsets that differ significantly in phenotype, gene expression, and functions

A type of human skin dendritic cell marked by CD5 is associated with the development of inflammatory skin disease

Human dendritic cell subsets, ontogeny, and impact on HIV infection

Mapping the human DC lineage through the integration of high-dimensional techniques

Dendritic cells in hematological malignancies

Dendritic cells: nature and classification

Efficient migration of dendritic cells toward lymph node chemokines and induction of T(H)1 responses require maturation stimulus and apoptotic cell interaction

CCR7 governs skin dendritic cell migration under inflammatory and steady-state conditions

A missing link: engagements of dendritic cells in the pathogenesis of SARS-CoV-2 infections

Dendritic cells in COVID-19 immunopathogenesis: insights for a possible role in determining disease outcome

Dendritic cells and SARS-CoV-2 infection: still an unclarified connection

CD147-spike protein is a novel route for SARS-CoV-2 infection to host cells

Constitutive and induced expression of DC-SIGN on dendritic cell and macrophage subpopulations in situ and in vitro

Distinct roles for DC-SIGN+-dendritic cells and Langerhans cells in HIV-1 transmission

CD209L (L-SIGN) is a receptor for severe acute respiratory syndrome coronavirus

DC-SIGN and DC-SIGNR interact with the glycoprotein of Marburg virus and the S protein of severe acute respiratory syndrome coronavirus

pH-dependent entry of severe acute respiratory syndrome coronavirus is mediated by the spike glycoprotein and enhanced by dendritic cell transfer through DC-SIGN

Cellular entry of the SARS coronavirus

Attenuated interferon and proinflammatory response in SARS-CoV-2-infected human dendritic cells is associated with viral antagonism of STAT1 phosphorylation

Interaction of severe acute respiratory syndrome-associated coronavirus with dendritic cells

Antiviral activities of type I interferons to SARS-CoV-2 infection

Comparative replication and immune activation profiles of SARS-CoV-2 and SARS-CoV in human lungs: an ex vivo study with implications for the pathogenesis of COVID-19

Imbalanced host response to SARS-CoV-2 drives development of COVID-19

Inborn errors of type I IFN immunity in patients with life-threatening COVID-19

Autoantibodies against type I IFNs in patients with life-threatening COVID-19

IPC: professional type 1 interferon-producing cells and plasmacytoid dendritic cell precursors

SARS-CoV-2 induces human plasmacytoid predendritic cell diversification via UNC93B and IRAK4

SARS-CoV-2 infection induces mixed M1/M2 phenotype in circulating monocytes and alterations in both dendritic cell and monocyte subsets

Immunological and inflammatory profiles during acute and convalescent phases of severe/ critically ill COVID-19 patients

Major alterations in the mononuclear phagocyte landscape associated with COVID-19 severity

A single-cell atlas of the peripheral immune response in patients with severe COVID-19

Differential redistribution of activated monocyte and dendritic cell subsets to the lung associates with severity of COVID-19

Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients

Single-cell RNA sequencing of blood antigen-presenting cells in severe COVID-19 reveals multi-process defects in antiviral immunity

Predictors of mortality for patients with COVID-19 pneumonia caused by SARS-CoV-2: a prospective cohort study

Suppressed T cell-mediated immunity in patients with COVID-19: a clinical retrospective study in Wuhan

Acute SARS-CoV-2 infection impairs dendritic cell and T cell responses

Disease-duration based comparison of subsets of immune cells in SARS CoV-2 infected patients presenting with mild or severe symptoms identifies prognostic markers for severity

Lessons from dermatology about inflammatory responses in Covid-19

Imaging mass cytometric analysis of postmortem tissues reveals dysregulated immune cell and cytokine responses in multiple organs of COVID-19 patients

Heightened innate immune responses in the respiratory tract of COVID-19 patients

Intestinal host response to SARS-CoV-2 infection and COVID-19 outcomes in patients with gastrointestinal symptoms

Impaired secretion of interferons by dendritic cells from aged subjects to influenza: role of histone modifications

Epigenetic regulator CXXC5 recruits DNA demethylase Tet2 to regulate TLR7/9-elicited IFN response in pDCs

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

Considering how biological sex impacts immune responses and COVID-19 outcomes

Estrogen receptor-dependent regulation of dendritic cell development and function

Management of anaphylaxis due to COVID-19 vaccines in the elderly

Role of dendritic cells in inflammation and loss of tolerance in the elderly

Age and immunity: what is "immunosenescence

Aging impairs the ability of conventional dendritic cells to cross-prime CD8 + T cells upon stimulation with a TLR7 ligand

Health, income and poverty: evidence from China's rural household survey

COVID-19 in children, pregnancy and neonates: a review of epidemiologic and clinical features

Could antigen presenting cells represent a protective element during SARS-CoV-2 infection in children? Pathogens

Is the developmentally immature immune response in paediatric sepsis a recapitulation of immune tolerance?

Peripheral immunophenotypes in children with multisystem inflammatory syndrome associated with SARS-CoV-2 infection

Mapping systemic inflammation and antibody responses in multisystem inflammatory syndrome in children (MIS-C)

Plasmacytoid dendritic cells depletion and elevation of IFN-gamma dependent chemokines CXCL9 and CXCL10 in children with multisystem inflammatory syndrome

Considerations on biologicals for patients with allergic disease in times of the COVID-19 pandemic: an EAACI statement

Association of respiratory allergy, asthma, and expression of the SARS-CoV-2 receptor ACE2

Targeting antiviral pathways for treatment of allergic diseases

Nasal epithelial barrier dysfunction increases sensitization and mast cell degranulation in the absence of allergic inflammation

Interferon at the crossroads of allergy and viral infections

How rhinovirus infections cause exacerbations of asthma

Effects of omalizumab on rhinovirus infections, illnesses, and exacerbations of asthma

Biologicals in allergic diseases and asthma: toward personalized medicine and precision health: highlights of the 3rd EAACI master class on biologicals

Preseasonal treatment with either omalizumab or an inhaled corticosteroid boost to prevent fall asthma exacerbations

Management of severe asthma: a European respiratory society/American thoracic society guideline

Insights into the immuno-pathogenesis of acute respiratory distress syndrome

COVID-19 pandemic and allergen immunotherapy -an EAACI survey

COVID-19 vaccine: a comprehensive status report

A guide to vaccinology: from basic principles to new developments

Dendritic cell-based immunotherapy

Personalized dendritic cell vaccines-recent breakthroughs and encouraging clinical results

Dendritic cell-based therapeutic cancer vaccines: past, present and future

Dendritic cells as pharmacological tools for cancer immunotherapy

Natural human plasmacytoid dendritic cells induce antigen-specific T-cell responses in melanoma patients

Targeting dendritic cells in vivo for cancer therapy

Targeting C-type lectin receptors: a highcarbohydrate diet for dendritic cells to improve cancer vaccines

Targeting dendritic cells: a promising strategy to improve vaccine effectiveness

Nanoparticle vaccines against infectious diseases

Nanoparticle vaccines

Nanoparticle-mediated combinatorial targeting of multiple human dendritic cell (DC) subsets leads to enhanced T cell activation via IL-15-dependent DC crosstalk

Safety and efficacy of the BNT162b2 mRNA covid-19 vaccine

Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine

EAACI statement on the diagnosis, management and prevention of severe allergic reactions to COVID-19 vaccines

Vaccines and allergic reactions: the past, the current COVID-19 pandemic, and future perspectives

How to cite this article

A bird's eye view on the role of dendritic cells in SARS-CoV-2 infection: Perspectives for immune-based vaccines