The role of IL-17A/IL-17RA and lung injuries in children with lethal non-pandemic acute viral pneumonia

Azevedo, Marina Luise Viola de; Malaquias, Minéia Alessandra Scaranello; Paula, Caroline Busatta Vaz de; Souza, Cleber Machado de; Júnior, Victor Horácio Costa; Raboni, Sônia Mara; Halila, Renata; Rosendo, Giuliana; Gozzo, Priscilla do Carmo; Carmo, Leticia Arianne Panini do; Neto, Plínio Cézar; Nagashima, Seigo; Noronha, Lúcia de

doi:10.1016/j.imbio.2020.151981

Cited by 4 publications

(8 citation statements)

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“…33,34 Many clinical studies link IL-17A-mediated neutrophilia to the severity of FLU-, RV-and RSV-induced lung disease. [35][36][37] Interestingly, Habibi et al demonstrated that even before viral exposure, people who had the pre-activated neutrophils (activated by IL-17A) in nasal samples could develop more severe symptom after infection with RSV. 38 This indicated that IL-17Aneutrophils axis is the key immune/inflammatory regulator in respiratory infection.…”

Section: Discussionmentioning

confidence: 99%

“…Increased IL‐17A levels are also associated with the recruitment and maintenance of neutrophils in the lung during viral infection, a cell type linked to induction of viral‐induced immunopathology 33,34 . Many clinical studies link IL‐17A‐mediated neutrophilia to the severity of FLU‐, RV‐ and RSV‐induced lung disease 35–37 . Interestingly, Habibi et al demonstrated that even before viral exposure, people who had the pre‐activated neutrophils (activated by IL‐17A) in nasal samples could develop more severe symptom after infection with RSV 38 .…”

Section: Discussionmentioning

confidence: 99%

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IL‐17A is a common and critical driver of impaired lung function and immunopathology induced by influenza virus, rhinovirus and respiratory syncytial virus

et al. 2021

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Background and objective: Influenza virus (FLU), rhinovirus (RV) and respiratory syncytial virus (RSV) are the most common acute respiratory infections worldwide. Infection can cause severe health outcomes, while therapeutic options are limited, primarily relieving symptoms without attenuating the development of lesions or impaired lung function. We therefore examined the inflammatory response to these infections with the intent to identify common components that are critical drivers of immunopathogenesis and thus represent potential therapeutic targets. Methods: BALB/c mice were infected with FLU, RV or RSV, and lung function, airway inflammation and immunohistopathology were measured over a 10-day period. Anti-IL-17A mAb was administered to determine the impact of attenuating this cytokine's function on the development and severity of disease. Results: All three viruses induced severe airway constriction and inflammation at 2 days post-infection (dpi). However, only FLU induced prolonged inflammation till 10 dpi. Increased IL-17A expression was correlated with the alterations in lung function and its persistence. Neutralization of IL-17A did not affect the viral replication but led to the resolution of airway hyperresponsiveness. Furthermore, anti-IL-17A treatment resulted in reduced infiltration of neutrophils (in RV-and FLU-infected mice at 2 dpi) and lymphocytes (in RSV-infected mice at 2 dpi and FLU-infected mice at 10 dpi), and attenuated the severity of immunopathology. Conclusion: IL-17A is a common pathogenic molecule regulating disease induced by three prevalent respiratory viruses. Targeting the IL-17A pathway may provide a unified approach to the treatment of these respiratory infections alleviating both inflammation-induced lesions and difficulties in breathing.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

IL‐17A is a common and critical driver of impaired lung function and immunopathology induced by influenza virus, rhinovirus and respiratory syncytial virus

et al. 2021

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“…These samples were obtained from 193 pediatric cases involving necropsy (occurring between 1960 and 2004) and whose cause of death was lethal non-pandemic acute pneumonia (Baurakiades et al 2014 ; Chong et al 2009 ; de Souza Costa et al 2014 ; do Carmo Debur et al, 2010 ). All 193 cases had already been tested for the presence of respiratory syncytial virus (RSV), adenovirus (AdV), parainfluenza type 1, 2 or 3 (PIV1, PIV2, and PIV3) and Influenza type A and type B (FLUA and FLUB) throughout immunohistochemistry (Azevedo et al, 2020 ; Baurakiades et al 2014 ; Chong et al 2009 ; de Souza Costa et al 2014 ; do Carmo Debur et al, 2010 ). Sixty-eight cases tested positive for the virus.…”

Section: Methodsmentioning

confidence: 99%

“…Incubations with the secondary antibody (Dako Advance™ HRP System, DakoCytomation, Inc., CA, USA) were carried out for 30 min. Incubations with 3,3'-diaminobenzidine and hydrogen peroxide substrate (DakoCytomation, Inc., CA, USA) were performed for 3 min to visualize positive staining (Azevedo et al, 2020 ).…”

Section: Methodsmentioning

confidence: 99%

“…When analyzing inflammatory mediators and outcomes, higher serum levels of IL-17A collected 24 h after hospital admission was associated with a higher 28-day survival rate (Almansa et al 2011 ). In addition, FLUA infection is related to increased expression of IL17-A/IL-17RA in lung tissue (Azevedo et al ., 2020 ). There is a duality between the protective and pathological function of IL-17A and single nucleotide polymorphisms (SNPs), which can modify the evolution and outcome of FLUA virus infection (Bermejo-Martin et al, 2009 ; To et al 2010 ; Sahu et al 2021 ).…”

Section: Introductionmentioning

confidence: 99%

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The role of IL17 and IL17RA polymorphisms in lethal pandemic acute viral pneumonia (Influenza A virus H1N1 subtype)

et al. 2023

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Background The cytokines play an essential role in acute inflammatory processes, and the IL-17 may be responsible for ambiguous aspects, and the correlation with genetic polymorphisms could improve the search for this critical biomarker. Thus, this study aimed to evaluate the IL-17A and IL-17RA tissue expression and the polymorphisms that codified these proteins in a population that died of pandemic Influenza A virus H1N1 subtype compared to a non-pandemic Influenza virus population. Methods Necropsy lung samples immunohistochemistry was performed to assess the presence of IL-17A and IL-17RA in the pulmonary tissue. Eight single nucleotide polymorphisms were genotyped using TaqMan® technology. Results The Influenza A H1N1 pandemic group had higher tissue expression of IL-17A, higher neutrophil recruitment and shorter survival time between admission and death. Three single nucleotide polymorphisms conferred risk for pandemic influenza A H1N1, the AA genotype of rs3819025 G/A, the CC genotype of rs2241044 A/C, and the TT genotype of rs 2,241,043 C/T. Conclusions One IL17A polymorphism (rs381905) and two IL17RA polymorphisms (rs2241044 and rs2241043) represented biomarkers of worse prognosis in the population infected with pandemic influenza A H1N1. The greater tissue expression of IL-17A shows a Th17 polarization and highlights the aggressiveness of the pandemic influenza virus with its duality in the protection and pathogenesis of the pulmonary infectious process.

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A comprehensive network map of IL-17A signaling pathway

Rex

Dagamajalu

Gouda

et al. 2022

J. Cell Commun. Signal.

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Interleukin-17A (IL-17A) is one of the member of IL-17 family consisting of other five members (IL-17B to IL-17F). The Gamma delta (γδ) T cells and T helper 17 (Th17) cells are the major producers of IL-17A. Aberrant signaling by IL-17A has been implicated in the pathogenesis of several autoimmune diseases including idiopathic pulmonary fibrosis, acute lung injury, chronic airway diseases, and cancer. Activation of the IL-17A/IL-17 receptor A (IL-17RA) system regulates phosphoinositide 3-kinase/AKT serine/threonine kinase/mammalian target of rapamycin (PI3K/AKT/mTOR), mitogen-activated protein kinases (MAPKs) and activation of nuclear factor-κB (NF-κB) mediated signaling pathways. The IL-17RA activation orchestrates multiple downstream signaling cascades resulting in the release of pro-inflammatory cytokines such as interleukins (IL)-1β, IL-6, and IL-8, chemokines (C-X-C motif) and promotes neutrophil-mediated immune response. Considering the biomedical importance of IL-17A, we developed a pathway resource of signaling events mediated by IL-17A/IL-17RA in this study. The curation of literature data pertaining to the IL-17A system was performed manually by the NetPath criteria. Using data mined from the published literature, we describe an integrated pathway reaction map of IL-17A/IL-17RA consisting of 114 proteins and 68 reactions. That includes detailed information on IL-17A/IL-17RA mediated signaling events of 9 activation/inhibition events, 17 catalysis events, 3 molecular association events, 68 gene regulation events, 109 protein expression events, and 6 protein translocation events. The IL-17A signaling pathway map data is made freely accessible through the WikiPathways Database (https:// www. wikip athwa ys. org/ index. php/ Pathw ay: WP5242).

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The role of IL-17A/IL-17RA and lung injuries in children with lethal non-pandemic acute viral pneumonia

Cited by 4 publications

References 61 publications

IL‐17A is a common and critical driver of impaired lung function and immunopathology induced by influenza virus, rhinovirus and respiratory syncytial virus

IL‐17A is a common and critical driver of impaired lung function and immunopathology induced by influenza virus, rhinovirus and respiratory syncytial virus

The role of IL17 and IL17RA polymorphisms in lethal pandemic acute viral pneumonia (Influenza A virus H1N1 subtype)

A comprehensive network map of IL-17A signaling pathway

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