Regulation of angiotensin-converting enzyme 2 isoforms by type 2 inflammation and viral infection in human airway epithelium

Stocker, Nino; Radzikowska, Urszula; Tan, Ge; Huang, Mengting; Ding, Mei; Akdiş, Cezmi A.; Sokołowska, Milena

doi:10.1016/j.mucimm.2022.12.001

Cited by 16 publications

(7 citation statements)

References 73 publications

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“…The role of type 2 cytokines in viral immunity is complex. IL-13 has been shown to decrease expression of the SCV2 entry receptor ACE2 on human bronchial epithelial cells ( 68 , 69 ) and limit SCV2 infection in vitro ( 70 , 71 ), suggesting that preexisting type 2 inflammation may be beneficial rather than detrimental to subsequent SCV2 infections. Type 2 asthma does not appear to increase risk of COVID-19 ( 72 , 73 ).…”

Section: Discussionmentioning

confidence: 99%

Exposure to lung-migrating helminth protects against murine SARS-CoV-2 infection through macrophage-dependent T cell activation

et al. 2023

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Helminth endemic regions report lower COVID-19 morbidity and mortality. Here, we show that lung remodeling from a prior infection with a lung-migrating helminth, Nippostrongylus brasiliensis , enhances viral clearance and survival of human-ACE2 transgenic mice challenged with SARS-CoV-2 (SCV2). This protection is associated with a lymphocytic infiltrate, including increased accumulation of pulmonary SCV2-specific CD8 + T cells, and anti-CD8 antibody depletion abrogated the N. brasiliensis– mediated reduction in viral loads. Pulmonary macrophages with a type 2 transcriptional and epigenetic signature persist in the lungs of N. brasiliensis –exposed mice after clearance of the parasite and establish a primed environment for increased CD8 + T cell recruitment and activation. Accordingly, depletion of macrophages ablated the augmented viral clearance and accumulation of CD8 + T cells driven by prior N. brasiliensis infection. Together, these findings support the concept that lung-migrating helminths can limit disease severity during SCV2 infection through macrophage-dependent enhancement of antiviral CD8 + T cell responses.

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Section: Discussionmentioning

confidence: 99%

Exposure to lung-migrating helminth protects against murine SARS-CoV-2 infection through macrophage-dependent T cell activation

et al. 2023

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“…The salivary gland also plays a major role as an effector site to produce T-cell-dependent antigen-specific oral IgA response. ACE2 receptors on highly differentiated epithelial cells are also strongly associated with cytokine levels in these tissues (23,24). Furthermore, mouse models have demonstrated that the resident microbiota on mucosal surfaces can protect against rotavirus infections (25), and it has been suggested to impact SARS-CoV-2 infections(26).…”

Section: Discussionmentioning

confidence: 99%

Host-Microbiome Associations in Saliva Predict COVID-19 Severity

Alqaderi

Altabtbaei

Espinoza

et al. 2023

Preprint

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Established evidence indicates that oral microbiota plays a crucial role in modulating host immune responses to viral infection. Following Severe Acute Respiratory Syndrome Coronavirus 2, SARS-CoV-2, there are coordinated microbiome and inflammatory responses within the mucosal and systemic compartments that are unknown. The specific roles that the oral microbiota and inflammatory cytokines play in the pathogenesis of COVID-19 are yet to be explored. We evaluated the relationships between the salivary microbiome and host parameters in different groups of COVID-19 severity based on their Oxygen requirement. Saliva and blood samples (n = 80) were collected from COVID-19 and from non-infected individuals. We characterized the oral microbiomes using 16S ribosomal RNA gene sequencing and evaluated saliva and serum cytokines using Luminex multiplex analysis. Alpha diversity of the salivary microbial community was negatively associated with COVID-19 severity. Integrated cytokine evaluations of saliva and serum showed that the oral host response was distinct from the systemic response. The hierarchical classification of COVID-19 status and respiratory severity using multiple modalities separately (i.e., microbiome, salivary cytokines, and systemic cytokines) and simultaneously (i.e., multi-modal perturbation analyses) revealed that the microbiome perturbation analysis was the most informative for predicting COVID-19 status and severity, followed by the multi-modal. Our findings suggest that oral microbiome and salivary cytokines may be predictive of COVID-19 status and severity, whereas atypical local mucosal immune suppression and systemic hyperinflammation provide new cues to understand the pathogenesis in immunologically naive populations.

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“…Energy producing processes such as glycolysis and mitochondrial oxidative phosphorylation (OXPHOS) interconnect with the tricarboxylic acid cycle, fatty acid oxidation, fatty acid synthesis, glutaminolysis, nucleic acid synthesis and provide metabolic cues to cell proliferation, migration, and function [34,35]. SARS-CoV-2 infects multiple cell types mainly via angiotensin-converting enzyme 2 (ACE2) [36][37][38][39] and inhibits expression of genes encoding all five OXPHOS complexes, as demonstrated in nasopharyngeal samples of infected versus non-infected individuals [40] and human respiratory epithelium [41]. In autopsy tissues from COVID-19 patients, a similar downregulation of OXPHOS encoding genes was found in the heart, kidney, and liver [40].…”

Section: Immune Metabolism In Long Covidmentioning

confidence: 99%

Immune Mechanisms Underpinning Long COVID: Collegium Internationale Allergologicum Update 2024

Untersmayr,

Venter,

Smith

et al. 2024

Int Arch Allergy Immunol

Self Cite

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Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can result in a prolonged multisystem disorder termed long COVID, which may affect up to 10% of people following coronavirus disease 2019 (COVID-19). It is currently unclear why certain individuals do not fully recover following SARS-CoV-2 infection. Summary: In this review, we examine immunological mechanisms that may underpin the pathophysiology of long COVID. These mechanisms include an inappropriate immune response to acute SARS-CoV-2 infection, immune cell exhaustion, immune cell metabolic reprogramming, a persistent SARS-CoV-2 reservoir, reactivation of other viruses, inflammatory responses impacting the central nervous system, autoimmunity, microbiome dysbiosis, and dietary factors. Key Messages: Unfortunately, the currently available diagnostic and treatment options for long COVID are inadequate, and more clinical trials are needed that match experimental interventions to underlying immunological mechanisms.

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Regulation of angiotensin-converting enzyme 2 isoforms by type 2 inflammation and viral infection in human airway epithelium

Cited by 16 publications

References 73 publications

Exposure to lung-migrating helminth protects against murine SARS-CoV-2 infection through macrophage-dependent T cell activation

Exposure to lung-migrating helminth protects against murine SARS-CoV-2 infection through macrophage-dependent T cell activation

Host-Microbiome Associations in Saliva Predict COVID-19 Severity

Immune Mechanisms Underpinning Long COVID: Collegium Internationale Allergologicum Update 2024

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