Alveolar Neutrophilic Recruitment in COVID-19 May Not be Mediated by Th17 Response

Abstract Introduction: The COVID-19 current pandemic disease differs from the H1N1pdm09 caused by Influenza A virus H1N1 subtype, by how it induces a pro-inflammatory response in infected lungs. Objective: Investigate the role of Th17 response in the pathogenesis of COVID-19 injury by analyzing the tissue expression of interleukins 8 and 17A and the neutrophils in lung samples of patients who die of COVID-19, comparing to H1N1pdm09. Study design and post-mortem results: Six lung samples from patients SARS-CoV-2 infected (COVID-19 group), and ten lung samples from adults who died from H1N1pdm09 (H1N1 group), were tested. A control group was also added to the study. H&E slides were used for neutrophils scoring. The tissue expression of IL-8 and IL-17A was identified by immunohistochemistry. Tissue expression increasing of IL-17A and IL-8 and a higher number of neutrophils were identified in samples from the H1N1 group when compared to the COVID-19 group. Discussion: It is suggested that the SARS-CoV-2 virus evokes an exacerbated response of the host's immune system but differs from that observed in the H1N1pdm09 disease because it may not be trigger by Th17 response. With the low expression of IL-8, IL-17A, neutrophil recruitment to the site of infection becomes impaired, resulting in viral persistence. On the other hand, in the COVID-19 disease, the immune response by Th2 cells seems to be exacerbated, observed by the extent of the lung injury. This uncontrolled response and, mainly, the lack of a therapeutic target, culminates in disease progression and, consequently, in shorter survival time.

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IL-4/IL-13 Remodeling Pathway of Covid-19 Lung Injury

10.21203/rs.3.rs-34688/v2 ◽

2020 ◽

Author(s):

Caroline Busatta Vaz de Paula ◽

Marina Luise Viola Azevedo ◽

Seigo Nagashima ◽

Ana Paula Camargo Martins ◽

Mineia Alessandra Scaranello Malaquias ◽

...

Keyword(s):

Lung Injury ◽

Transforming Growth Factor Beta ◽

Influenza A ◽

Transforming Growth Factor ◽

Diffuse Alveolar Damage ◽

Tissue Expression ◽

Lung Damage ◽

Control Group ◽

M2 Macrophages ◽

Th17 Response

Abstract Background: The COVID-19 fatality rate is high when compared to the H1N1pdm09 (pandemic Influenza A virus H1N1 subtype) rate, and although both cause an aggravated inflammatory response, the differences in the mechanisms of both pandemic pneumonias need clarification.Objective: To analyze tissue expression of interleukins 4, 13, (IL-4, IL-13), transforming growth factor-beta (TGF-β), and the number of M2 macrophages (Sphingosine-1) in patients who died by COVID-19, comparing with cases of severe pneumopathy caused by H1N1pdm09, and a control group without lung injury.Methods: Six lung biopsy samples of patients who died of SARS-CoV-2 (COVID-19 group) were used and compared with ten lung samples of adults who died from a severe infection of H1N1pdm09 (H1N1 group) and eleven samples of patients who died from different causes without lung injury (CONTROL group). The expression of IL-4, IL-13, TGF-β, and M2 macrophages score (Sphingosine-1) were identified through immunohistochemistry (IHC).Results and conclusion: Significantly higher IL-4 tissue expression and Sphingosine-1 in M2 macrophages was observed in the COVID-19 group when compared to both the H1N1 and the CONTROL groups. Different mechanism of diffuse alveolar damage (DAD) in SARS-CoV-2 compared to H1N1pdm09 infections were observed. IL-4 expression and lung remodeling are phenomena observed in both SARS-COV-2 and H1N1pdm09. However, SARS-CoV-2 seems to promote lung damage through different mechanisms, such as the scarce participation Th1/Th17 response and the higher participation of the Th2. The understanding and management of the aggravated and ineffective immune response elicited by SARS-CoV-2 merits further clarification to improve treatments propose.

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Lung Neutrophilic Recruitment and IL-8/IL-17A Tissue Expression in COVID-19

Frontiers in Immunology ◽

10.3389/fimmu.2021.656350 ◽

2021 ◽

Vol 12 ◽

Author(s):

Marina Luise Viola Azevedo ◽

Aline Cristina Zanchettin ◽

Caroline Busatta Vaz de Paula ◽

Jarbas da Silva Motta Júnior ◽

Mineia Alessandra Scaranello Malaquias ◽

...

Keyword(s):

Immune System ◽

Inflammatory Response ◽

Influenza A ◽

Risk Allele ◽

Tissue Expression ◽

H1n1 Subtype ◽

Post Mortem ◽

Virus H1n1 ◽

Genotype Frequencies ◽

Hematoxylin And Eosin

The new SARS-CoV-2 virus differs from the pandemic Influenza A virus H1N1 subtype (H1N1pmd09) how it induces a pro-inflammatory response in infected patients. This study aims to evaluate the involvement of SNPs and tissue expression of IL-17A and the neutrophils recruitment in post-mortem lung samples from patients who died of severe forms of COVID-19 comparing to those who died by H1N1pdm09. Twenty lung samples from patients SARS-CoV-2 infected (COVID-19 group) and 10 lung samples from adults who died from a severe respiratory H1N1pdm09 infection (H1N1 group) were tested. The tissue expression of IL-8/IL-17A was identified by immunohistochemistry, and hematoxylin and eosin (H&E) stain slides were used for neutrophil scoring. DNA was extracted from paraffin blocks, and genotyping was done in real time-PCR for two IL17A target polymorphisms. Tissue expression increasing of IL-8/IL-17A and a higher number of neutrophils were identified in samples from the H1N1 group compared to the COVID-19 group. The distribution of genotype frequencies in the IL17A gene was not statistically significant between groups. However, the G allele (GG and GA) of rs3819025 was correlated with higher tissue expression of IL-17A in the COVID-19 group. SARS-CoV-2 virus evokes an exacerbated response of the host’s immune system but differs from that observed in the H1N1pdm09 infection since the IL-8/IL-17A tissue expression, and lung neutrophilic recruitment may be decreased. In SNP rs3819025 (G/A), the G allele may be considered a risk allele in the patients who died for COVID-19.

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IL-4/IL-13 Remodeling Pathway of Covid-19 Lung Injury

10.21203/rs.3.rs-34688/v1 ◽

2020 ◽

Author(s):

Caroline Busatta Vaz de Paula ◽

Marina Luise Viola Azevedo ◽

Seigo Nagashima ◽

Ana Paula Camargo Martins ◽

Mineia Alessandra Scaranello Malaquias ◽

...

Keyword(s):

Lung Injury ◽

Transforming Growth Factor Beta ◽

Influenza A ◽

Transforming Growth Factor ◽

Diffuse Alveolar Damage ◽

Tissue Expression ◽

Lung Damage ◽

Control Group ◽

M2 Macrophages ◽

Th17 Response

Abstract Background: The COVID-19 fatality rate is high when compared to the H1N1pdm09 (pandemic Influenza A virus H1N1 subtype) rate, and although both cause an aggravated inflammatory response, the differences in the mechanisms of both pandemic pneumonias need clarification.Objective: To analyze tissue expression of interleukins 4, 13, (IL-4, IL-13), transforming growth factor-beta (TGF-β), and the number of M2 macrophages (Sphingosine-1) in patients who died by COVID-19, comparing with cases of severe pneumopathy caused by H1N1pdm09, and a control group without lung injury.Methods: Six lung biopsy samples of patients who died of SARS-CoV-2 (COVID-19 group) were used and compared with ten lung samples of adults who died from a severe infection of H1N1pdm09 (H1N1 group) and eleven samples of patients who died from different causes without lung injury (CONTROL group). The expression of IL-4, IL-13, TGF-β, and M2 macrophages score (Sphingosine-1) were identified through immunohistochemistry (IHC).Results and conclusion: Significantly higher IL-4 tissue expression and Sphingosine-1 in M2 macrophages was observed in the COVID-19 group when compared to both the H1N1 and the CONTROL groups. Different mechanism of diffuse alveolar damage (DAD) in SARS-CoV-2 compared to H1N1pdm09 infections were observed. IL-4 expression and lung remodeling are phenomena observed in both SARS-COV-2 and H1N1pdm09. However, SARS-CoV-2 seems to promote lung damage through different mechanisms, such as the scarce participation Th1/Th17 response and the higher participation of the Th2. The understanding and management of the aggravated and ineffective immune response elicited by SARS-CoV-2 merits further clarification to improve treatments propose.

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IL-4/IL-13 Remodeling Pathway of Covid-19 Lung Injury

10.21203/rs.3.rs-34688/v3 ◽

2020 ◽

Cited By ~ 1

Author(s):

Caroline Busatta Vaz de Paula ◽

Marina Luise Viola Azevedo ◽

Seigo Nagashima ◽

Ana Paula Camargo Martins ◽

Mineia Alessandra Scaranello Malaquias ◽

...

Keyword(s):

Lung Injury ◽

Transforming Growth Factor Beta ◽

Influenza A ◽

Transforming Growth Factor ◽

Diffuse Alveolar Damage ◽

Tissue Expression ◽

Lung Damage ◽

Control Group ◽

M2 Macrophages ◽

Th17 Response

Abstract Background: The COVID-19 fatality rate is high when compared to the H1N1pdm09 (pandemic Influenza A virus H1N1 subtype) rate, and although both cause an aggravated inflammatory response, the differences in the mechanisms of both pandemic pneumonias need clarification.Objective: To analyze tissue expression of interleukins 4, 13, (IL-4, IL-13), transforming growth factor-beta (TGF-β), and the number of M2 macrophages (Sphingosine-1) in patients who died by COVID-19, comparing with cases of severe pneumopathy caused by H1N1pdm09, and a control group without lung injury.Methods: Six lung biopsy samples of patients who died of SARS-CoV-2 (COVID-19 group) were used and compared with ten lung samples of adults who died from a severe infection of H1N1pdm09 (H1N1 group) and eleven samples of patients who died from different causes without lung injury (CONTROL group). The expression of IL-4, IL-13, TGF-β, and M2 macrophages score (Sphingosine-1) were identified through immunohistochemistry (IHC).Results and conclusion: Significantly higher IL-4 tissue expression and Sphingosine-1 in M2 macrophages was observed in the COVID-19 group when compared to both the H1N1 and the CONTROL groups. Different mechanism of diffuse alveolar damage (DAD) in SARS-CoV-2 compared to H1N1pdm09 infections were observed. IL-4 expression and lung remodeling are phenomena observed in both SARS-COV-2 and H1N1pdm09. However, SARS-CoV-2 seems to promote lung damage through different mechanisms, such as the scarce participation Th1/Th17 response and the higher participation of the Th2. The understanding and management of the aggravated and ineffective immune response elicited by SARS-CoV-2 merits further clarification to improve treatments propose.

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IL-4/IL-13 remodeling pathway of COVID-19 lung injury

Scientific Reports ◽

10.1038/s41598-020-75659-5 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Caroline Busatta Vaz de Paula ◽

Marina Luise Viola de Azevedo ◽

Seigo Nagashima ◽

Ana Paula Camargo Martins ◽

Mineia Alessandra Scaranello Malaquias ◽

...

Keyword(s):

Lung Injury ◽

Transforming Growth Factor Beta ◽

Influenza A ◽

Transforming Growth Factor ◽

Diffuse Alveolar Damage ◽

Tissue Expression ◽

Lung Damage ◽

Control Group ◽

M2 Macrophages ◽

Th17 Response

Abstract The COVID-19 fatality rate is high when compared to the H1N1pdm09 (pandemic Influenza A virus H1N1 subtype) rate, and although both cause an aggravated inflammatory response, the differences in the mechanisms of both pandemic pneumonias need clarification. Thus, our goal was to analyze tissue expression of interleukins 4, 13, (IL-4, IL-13), transforming growth factor-beta (TGF-β), and the number of M2 macrophages (Sphingosine-1) in patients who died by COVID-19, comparing with cases of severe pneumopathy caused by H1N1pdm09, and a control group without lung injury. Six lung biopsy samples of patients who died of SARS-CoV-2 (COVID-19 group) were used and compared with ten lung samples of adults who died from a severe infection of H1N1pdm09 (H1N1 group) and eleven samples of patients who died from different causes without lung injury (CONTROL group). The expression of IL-4, IL-13, TGF-β, and M2 macrophages score (Sphingosine-1) were identified through immunohistochemistry (IHC). Significantly higher IL-4 tissue expression and Sphingosine-1 in M2 macrophages were observed in the COVID-19 group compared to both the H1N1 and the CONTROL groups. A different mechanism of diffuse alveolar damage (DAD) in SARS-CoV-2 compared to H1N1pdm09 infections were observed. IL-4 expression and lung remodeling are phenomena observed in both SARS-CoV-2 and H1N1pdm09. However, SARS-CoV-2 seems to promote lung damage through different mechanisms, such as the scarce participation Th1/Th17 response and the higher participation of the Th2. Understanding and managing the aggravated and ineffective immune response elicited by SARS-CoV-2 merits further clarification to improve treatments propose.

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Host-cell dependent role of phosphorylated keratin 8 during influenza A/NWS/33 virus (H1N1) infection in mammalian cells

Virus Research ◽

10.1016/j.virusres.2021.198333 ◽

2021 ◽

Vol 295 ◽

pp. 198333

Author(s):

Flora De Conto ◽

Francesca Conversano ◽

Sergey V. Razin ◽

Silvana Belletti ◽

Maria Cristina Arcangeletti ◽

...

Keyword(s):

Host Cell ◽

Mammalian Cells ◽

Influenza A ◽

Virus H1n1 ◽

H1n1 Infection ◽

Keratin 8

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Possible Roles of IL-33 in the Innate-Adaptive Immune Crosstalk of Psoriasis Pathogenesis

Mediators of Inflammation ◽

10.1155/2019/7158014 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10 ◽

Cited By ~ 1

Author(s):

Serafinella Patrizia Cannavò ◽

Lucrezia Bertino ◽

Eleonora Di Salvo ◽

Valeria Papaianni ◽

Elvira Ventura-Spagnolo ◽

...

Keyword(s):

Th2 Cells ◽

Future Research ◽

Publication Date ◽

Th17 Response ◽

Adaptive Immune ◽

The Core ◽

Biological Variables ◽

St2 Receptor ◽

Neutrophil Response

Background. IL-33 belongs to the IL-1 family, playing a role in several biologic processes as well as in the pathogenesis of different diseases, including skin pathologies. It acts as an alarmin, released by damaged cells. Binding to a ST2 receptor, it stimulates many immune cells such as ILC2 and Th2 cells. IL-33/ST2 axis seems to be involved in Th17 response. According to this, a review was performed to analyze if IL-33 even interplay in the onset of psoriasis, a Th1/Th17 inflammatory disease. Methods. Data obtained from the included articles are study author name, publication date, group studied, clinical and biological variables, laboratory tests, and outcome of interest of the study. Results. Data are obtained from the 19 studies identified, which assessed the association between IL-33 and psoriasis. Discussion. It seems to promote the innate-adaptive immune crosstalk: it could induce mast cells and neutrophil response after being released by injured keratinocytes and after stimulation by some cytokines, in particular TNFα, INFγ, and IL-17A. In addition, it seems to be involved from the onset of disease to the development of comorbidities, as psoriatic arthritis. Conclusion. The core of the future research on psoriasis could be to fully understand the role of this complex cytokine, in order also to find a new therapeutic approach.

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