The Experts below are selected from a list of 466221 Experts worldwide ranked by ideXlab platform
Donald C Mcmillan - One of the best experts on this subject based on the ideXlab platform.
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comparison of the prognostic value of measures of the tumor Inflammatory Cell infiltrate and tumor associated stroma in patients with primary operable colorectal cancer
OncoImmunology, 2016Co-Authors: James H Park, Joanne Edwards, Donald C Mcmillan, Paul G Horgan, Campbell S D RoxburghAbstract:The aim of the present study was to compare the clinical utility of two measures of the Inflammatory Cell infiltrate - a HE Im0/1: from 71% to 38%, both p < 0.001) but not those with a strong Inflammatory infiltrate. On multivariate analysis, only Immunoscore (HR 0.44, p < 0.001) and TSP (HR 2.04, p < 0.001) were independently associated with CSS. These results suggest that the prognostic value of an immunohistochemistry-based assessment of the Inflammatory Cell infiltrate is superior to H&E-based assessment in patients undergoing resection of stage I-III CRC. Furthermore, assessment of the tumor-associated stroma, using TSP, further improves prediction of outcome.
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comparison of the prognostic value of measures of the tumor Inflammatory Cell infiltrate and tumor associated stroma in patients with primary operable colorectal cancer
OncoImmunology, 2016Co-Authors: James H Park, Joanne Edwards, Donald C Mcmillan, Paul G Horgan, Campbell S D RoxburghAbstract:ABSTRACTThe aim of the present study was to compare the clinical utility of two measures of the Inflammatory Cell infiltrate — a H&E-based assessment of the generalized Inflammatory Cell infiltrate (the Klintrup-Makinen (KM) grade), and an immunohistochemistry-based assessment of combined CD3+ and CD8+ T-Cell density (the “Immunoscore”), in conjunction with assessment of the tumor stroma percentage (TSP) in patients undergoing resection of stage I-III colorectal cancer (CRC). Two hundred and forty-six patients were identified from a prospectively maintained database of CRC resections in a single surgical unit. Assessment of KM grade and TSP was performed using full H&E sections. CD3+ and CD8+ T-Cell density was assessed on full sections and the Immunoscore calculated. KM grade and Immunoscore were strongly associated (p < 0.001). KM grade stratified cancer-specific survival (CSS) from 88% to 66% (p = 0.002) and Immunoscore from 93% to 61% (p < 0.001). Immunoscore further stratified survival of patients in...
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assessment of the tumor Inflammatory Cell infiltrate in preoperative colonoscopic biopsies of patients with primary operable colorectal cancer
Journal of Clinical Oncology, 2015Co-Authors: James H Park, Donald C Mcmillan, David Mansouri, Clare Orange, Paul G Horgan, Campbell S D RoxburghAbstract:637 Background: The tumor Inflammatory Cell infiltrate is an important and potentially modifiable determinant of outcome in colorectal cancer (CRC). Although a weak Inflammatory infiltrate is associated with poor prognosis independent of TNM stage, identifying such patients prior to surgery is problematic. The aim of the present study was to compare the tumor Inflammatory Cell infiltrate in matched preoperative colonoscopic tumor biopsies and resected tumor specimens from patients undergoing primary elective resection of CRC. Methods: Using an automated scoring system (nuclear h-score) CD3+ T-lymphocyte density was quantified in preoperative tumor biopsies of 76 patients undergoing elective resection of stage I-III CRC and compared to pathological characteristics and manual semi-quantitative (high vs. low) scoring of CD3+density within the invasive margin (IM) intraepithelial (IE) and cancer stroma (CS) compartments of resected tumor specimens. Results: The median h-score was 41 (range 14-85). Patients wi...
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the role of the tumour Inflammatory Cell infiltrate in predicting recurrence and survival in patients with primary operable breast cancer
Cancer Treatment Reviews, 2012Co-Authors: Zahra M A Mohammed, James J Going, Joanne Edwards, Donald C McmillanAbstract:Although the first studies highlighting the importance of the tumour Inflammatory Cell infiltrate were reported more than 80 years ago, the prognostic value of this response in breast cancer is still controversial. With the realisation of the importance of the Inflammatory response in determining tumour progression there has been renewed interest in establishing the relationship between the type, density and location of Inflammatory Cell infiltrate and survival in patients with primary operable breast cancer. The aim was to undertake a systematic review of the literature examining the evidence for the role of the tumour Inflammatory Cell infiltrate in predicting recurrence and survival in patients with primary operable breast cancer. A systematic review of published papers up to September 2011 was undertaken according to a pre-defined protocol (Fig. 1). A total of 66 independent studies (34,086 patients) were identified. It can be concluded from the review that despite the large number of studies and considerable effort over an extended period, the relationship between different aspects of tumour Inflammatory Cell infiltrate and outcome in primary operable breast cancer remains unclear. This is in large part due to the absence of methodological validation, underpowered studies (small sample size and sample subtype heterogeneity, insufficient follow-up) and the absence of validation datasets. Therefore, although there are tantalising examples of the potential of the tumour Inflammatory Cell infiltrate to improve risk stratification patients with operable breast cancer (personalised care), this has not yet been realised. Future studies with standardised methodology, large and homogenous groups, sufficient follow-up and validation datasets should be undertaken to unlock the potential of the tumour Inflammatory infiltrate to predict outcome in patients with primary operable breast cancer.
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the relationship between components of tumour Inflammatory Cell infiltrate and clinicopathological factors and survival in patients with primary operable invasive ductal breast cancer
British Journal of Cancer, 2012Co-Authors: Zahra M A Mohammed, James J Going, Joanne Edwards, Donald C Mcmillan, B Elsberger, J C DoughtyAbstract:The relationship between components of tumour Inflammatory Cell infiltrate and clinicopathological factors and survival in patients with primary operable invasive ductal breast cancer
R Subbarao K Malireddi - One of the best experts on this subject based on the ideXlab platform.
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synergism of tnf α and ifn γ triggers Inflammatory Cell death tissue damage and mortality in sars cov 2 infection and cytokine shock syndromes
Cell, 2021Co-Authors: Rajendra Karki, Min Zheng, Evan P Williams, Balaji Banoth, Bhesh Raj Sharma, Shraddha Tuladhar, Lillian Zalduondo, Parimal Samir, Balamurugan Sundaram, R Subbarao K MalireddiAbstract:COVID-19 is characterized by excessive production of pro-Inflammatory cytokines and acute lung damage associated with patient mortality. While multiple Inflammatory cytokines are produced by innate immune Cells during SARS-CoV-2 infection, we found that only the combination of TNF-α and IFN-γ induced Inflammatory Cell death characterized by Inflammatory Cell death, PANoptosis. Mechanistically, TNF-α and IFN-γ co-treatment activated the JAK/STAT1/IRF1 axis, inducing nitric oxide production and driving caspase-8/FADD-mediated PANoptosis. TNF-α and IFN-γ caused a lethal cytokine shock in mice that mirrors the tissue damage and inflammation of COVID-19, and inhibiting PANoptosis protected mice from this pathology and death. Furthermore, treating with neutralizing antibodies against TNF-α and IFN-γ protected mice from mortality during SARS-CoV-2 infection, sepsis, hemophagocytic lymphohistiocytosis, and cytokine shock. Collectively, our findings suggest that blocking the cytokine-mediated Inflammatory Cell death signaling pathway identified here may benefit patients with COVID-19 or other infectious and autoInflammatory diseases by limiting tissue damage/inflammation.
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synergism of tnf α and ifn γ triggers Inflammatory Cell death tissue damage and mortality in sars cov 2 infection and cytokine shock syndromes
bioRxiv, 2020Co-Authors: Rajendra Karki, Min Zheng, Evan P Williams, Balaji Banoth, Bhesh Raj Sharma, Shraddha Tuladhar, Lillian Zalduondo, Parimal Samir, Balamurugan Sundaram, R Subbarao K MalireddiAbstract:The COVID-19 pandemic has caused significant morbidity and mortality. Currently, there is a critical shortage of proven treatment options and an urgent need to understand the pathogenesis of multi-organ failure and lung damage. Cytokine storm is associated with severe inflammation and organ damage during COVID-19. However, a detailed molecular pathway defining this cytokine storm is lacking, and gaining mechanistic understanding of how SARS-CoV-2 elicits a hyperactive Inflammatory response is critical to develop effective therapeutics. Of the multiple Inflammatory cytokines produced by innate immune Cells during SARS-CoV-2 infection, we found that the combined production of TNF-α and IFN-γ specifically induced Inflammatory Cell death, PANoptosis, characterized by gasdermin-mediated pyroptosis, caspase-8-mediated apoptosis, and MLKL-mediated necroptosis. Deletion of pyroptosis, apoptosis, or necroptosis mediators individually was not sufficient to protect against Cell death. However, Cells deficient in both RIPK3 and caspase-8 or RIPK3 and FADD were resistant to this Cell death. Mechanistically, the JAK/STAT1/IRF1 axis activated by TNF-α and IFN-γ co-treatment induced iNOS for the production of nitric oxide. Pharmacological and genetic deletion of this pathway inhibited pyroptosis, apoptosis, and necroptosis in macrophages. Moreover, inhibition of PANoptosis protected mice from TNF-α and IFN-γ-induced lethal cytokine shock that mirrors the pathological symptoms of COVID-19. In vivo neutralization of both TNF-α and IFN-γ in multiple disease models associated with cytokine storm showed that this treatment provided substantial protection against not only SARS-CoV-2 infection, but also sepsis, hemophagocytic lymphohistiocytosis, and cytokine shock models, demonstrating the broad physiological relevance of this mechanism. Collectively, our findings suggest that blocking the cytokine-mediated Inflammatory Cell death signaling pathway identified here may benefit patients with COVID-19 or other cytokine storm-driven syndromes by limiting inflammation and tissue damage. The findings also provide a molecular and mechanistic description for the term cytokine storm. Additionally, these results open new avenues for the treatment of other infectious and autoInflammatory diseases and cancers where TNF-α and IFN-γ synergism play key pathological roles.
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impaired nlrp3 inflammasome activation pyroptosis leads to robust Inflammatory Cell death via caspase 8 ripk3 during coronavirus infection
Journal of Biological Chemistry, 2020Co-Authors: Min Zheng, Richard J. Webby, Rudragouda Channappanavar, Evan P Williams, R Subbarao K Malireddi, Rajendra Karki, Balaji Banoth, Amanda R Burton, Colleen B Jonsson, Thirumaladevi KannegantiAbstract:Coronaviruses have caused several zoonotic infections in the past two decades, leading to significant morbidity and mortality globally. Balanced regulation of Cell death and Inflammatory immune responses is essential to promote protection against coronavirus infection; however, the underlying mechanisms that control these processes remain to be resolved. Here we demonstrate that infection with the murine coronavirus mouse hepatitis virus (MHV) activated the NLRP3 inflammasome and Inflammatory Cell death in the form of PANoptosis. Deleting NLRP3 inflammasome components or the downstream Cell death executioner gasdermin D (GSDMD) led to an initial reduction in Cell death followed by a robust increase in the incidence of caspase-8- and receptor-interacting serine/threonine-protein kinase 3 (RIPK3)-mediated Inflammatory Cell deathafter coronavirus infection. Additionally, loss of GSDMD promoted robust NLRP3 inflammasome activation. Moreover, the amounts of some cytokines released during coronavirus infection were significantly altered in the absence of GSDMD. Altogether, our findings show that Inflammatory Cell death, PANoptosis, is induced by coronavirus infection and that impaired NLRP3 inflammasome function or pyroptosis can lead to negative consequences for the host. These findings may have important implications for studies of coronavirus-induced disease.
Joanne Edwards - One of the best experts on this subject based on the ideXlab platform.
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comparison of the prognostic value of measures of the tumor Inflammatory Cell infiltrate and tumor associated stroma in patients with primary operable colorectal cancer
OncoImmunology, 2016Co-Authors: James H Park, Joanne Edwards, Donald C Mcmillan, Paul G Horgan, Campbell S D RoxburghAbstract:The aim of the present study was to compare the clinical utility of two measures of the Inflammatory Cell infiltrate - a HE Im0/1: from 71% to 38%, both p < 0.001) but not those with a strong Inflammatory infiltrate. On multivariate analysis, only Immunoscore (HR 0.44, p < 0.001) and TSP (HR 2.04, p < 0.001) were independently associated with CSS. These results suggest that the prognostic value of an immunohistochemistry-based assessment of the Inflammatory Cell infiltrate is superior to H&E-based assessment in patients undergoing resection of stage I-III CRC. Furthermore, assessment of the tumor-associated stroma, using TSP, further improves prediction of outcome.
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comparison of the prognostic value of measures of the tumor Inflammatory Cell infiltrate and tumor associated stroma in patients with primary operable colorectal cancer
OncoImmunology, 2016Co-Authors: James H Park, Joanne Edwards, Donald C Mcmillan, Paul G Horgan, Campbell S D RoxburghAbstract:ABSTRACTThe aim of the present study was to compare the clinical utility of two measures of the Inflammatory Cell infiltrate — a H&E-based assessment of the generalized Inflammatory Cell infiltrate (the Klintrup-Makinen (KM) grade), and an immunohistochemistry-based assessment of combined CD3+ and CD8+ T-Cell density (the “Immunoscore”), in conjunction with assessment of the tumor stroma percentage (TSP) in patients undergoing resection of stage I-III colorectal cancer (CRC). Two hundred and forty-six patients were identified from a prospectively maintained database of CRC resections in a single surgical unit. Assessment of KM grade and TSP was performed using full H&E sections. CD3+ and CD8+ T-Cell density was assessed on full sections and the Immunoscore calculated. KM grade and Immunoscore were strongly associated (p < 0.001). KM grade stratified cancer-specific survival (CSS) from 88% to 66% (p = 0.002) and Immunoscore from 93% to 61% (p < 0.001). Immunoscore further stratified survival of patients in...
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the role of the tumour Inflammatory Cell infiltrate in predicting recurrence and survival in patients with primary operable breast cancer
Cancer Treatment Reviews, 2012Co-Authors: Zahra M A Mohammed, James J Going, Joanne Edwards, Donald C McmillanAbstract:Although the first studies highlighting the importance of the tumour Inflammatory Cell infiltrate were reported more than 80 years ago, the prognostic value of this response in breast cancer is still controversial. With the realisation of the importance of the Inflammatory response in determining tumour progression there has been renewed interest in establishing the relationship between the type, density and location of Inflammatory Cell infiltrate and survival in patients with primary operable breast cancer. The aim was to undertake a systematic review of the literature examining the evidence for the role of the tumour Inflammatory Cell infiltrate in predicting recurrence and survival in patients with primary operable breast cancer. A systematic review of published papers up to September 2011 was undertaken according to a pre-defined protocol (Fig. 1). A total of 66 independent studies (34,086 patients) were identified. It can be concluded from the review that despite the large number of studies and considerable effort over an extended period, the relationship between different aspects of tumour Inflammatory Cell infiltrate and outcome in primary operable breast cancer remains unclear. This is in large part due to the absence of methodological validation, underpowered studies (small sample size and sample subtype heterogeneity, insufficient follow-up) and the absence of validation datasets. Therefore, although there are tantalising examples of the potential of the tumour Inflammatory Cell infiltrate to improve risk stratification patients with operable breast cancer (personalised care), this has not yet been realised. Future studies with standardised methodology, large and homogenous groups, sufficient follow-up and validation datasets should be undertaken to unlock the potential of the tumour Inflammatory infiltrate to predict outcome in patients with primary operable breast cancer.
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the relationship between components of tumour Inflammatory Cell infiltrate and clinicopathological factors and survival in patients with primary operable invasive ductal breast cancer
British Journal of Cancer, 2012Co-Authors: Zahra M A Mohammed, James J Going, Joanne Edwards, Donald C Mcmillan, B Elsberger, J C DoughtyAbstract:The relationship between components of tumour Inflammatory Cell infiltrate and clinicopathological factors and survival in patients with primary operable invasive ductal breast cancer
Campbell S D Roxburgh - One of the best experts on this subject based on the ideXlab platform.
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comparison of the prognostic value of measures of the tumor Inflammatory Cell infiltrate and tumor associated stroma in patients with primary operable colorectal cancer
OncoImmunology, 2016Co-Authors: James H Park, Joanne Edwards, Donald C Mcmillan, Paul G Horgan, Campbell S D RoxburghAbstract:ABSTRACTThe aim of the present study was to compare the clinical utility of two measures of the Inflammatory Cell infiltrate — a H&E-based assessment of the generalized Inflammatory Cell infiltrate (the Klintrup-Makinen (KM) grade), and an immunohistochemistry-based assessment of combined CD3+ and CD8+ T-Cell density (the “Immunoscore”), in conjunction with assessment of the tumor stroma percentage (TSP) in patients undergoing resection of stage I-III colorectal cancer (CRC). Two hundred and forty-six patients were identified from a prospectively maintained database of CRC resections in a single surgical unit. Assessment of KM grade and TSP was performed using full H&E sections. CD3+ and CD8+ T-Cell density was assessed on full sections and the Immunoscore calculated. KM grade and Immunoscore were strongly associated (p < 0.001). KM grade stratified cancer-specific survival (CSS) from 88% to 66% (p = 0.002) and Immunoscore from 93% to 61% (p < 0.001). Immunoscore further stratified survival of patients in...
-
comparison of the prognostic value of measures of the tumor Inflammatory Cell infiltrate and tumor associated stroma in patients with primary operable colorectal cancer
OncoImmunology, 2016Co-Authors: James H Park, Joanne Edwards, Donald C Mcmillan, Paul G Horgan, Campbell S D RoxburghAbstract:The aim of the present study was to compare the clinical utility of two measures of the Inflammatory Cell infiltrate - a HE Im0/1: from 71% to 38%, both p < 0.001) but not those with a strong Inflammatory infiltrate. On multivariate analysis, only Immunoscore (HR 0.44, p < 0.001) and TSP (HR 2.04, p < 0.001) were independently associated with CSS. These results suggest that the prognostic value of an immunohistochemistry-based assessment of the Inflammatory Cell infiltrate is superior to H&E-based assessment in patients undergoing resection of stage I-III CRC. Furthermore, assessment of the tumor-associated stroma, using TSP, further improves prediction of outcome.
-
assessment of the tumor Inflammatory Cell infiltrate in preoperative colonoscopic biopsies of patients with primary operable colorectal cancer
Journal of Clinical Oncology, 2015Co-Authors: James H Park, Donald C Mcmillan, David Mansouri, Clare Orange, Paul G Horgan, Campbell S D RoxburghAbstract:637 Background: The tumor Inflammatory Cell infiltrate is an important and potentially modifiable determinant of outcome in colorectal cancer (CRC). Although a weak Inflammatory infiltrate is associated with poor prognosis independent of TNM stage, identifying such patients prior to surgery is problematic. The aim of the present study was to compare the tumor Inflammatory Cell infiltrate in matched preoperative colonoscopic tumor biopsies and resected tumor specimens from patients undergoing primary elective resection of CRC. Methods: Using an automated scoring system (nuclear h-score) CD3+ T-lymphocyte density was quantified in preoperative tumor biopsies of 76 patients undergoing elective resection of stage I-III CRC and compared to pathological characteristics and manual semi-quantitative (high vs. low) scoring of CD3+density within the invasive margin (IM) intraepithelial (IE) and cancer stroma (CS) compartments of resected tumor specimens. Results: The median h-score was 41 (range 14-85). Patients wi...
Rajendra Karki - One of the best experts on this subject based on the ideXlab platform.
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synergism of tnf α and ifn γ triggers Inflammatory Cell death tissue damage and mortality in sars cov 2 infection and cytokine shock syndromes
Cell, 2021Co-Authors: Rajendra Karki, Min Zheng, Evan P Williams, Balaji Banoth, Bhesh Raj Sharma, Shraddha Tuladhar, Lillian Zalduondo, Parimal Samir, Balamurugan Sundaram, R Subbarao K MalireddiAbstract:COVID-19 is characterized by excessive production of pro-Inflammatory cytokines and acute lung damage associated with patient mortality. While multiple Inflammatory cytokines are produced by innate immune Cells during SARS-CoV-2 infection, we found that only the combination of TNF-α and IFN-γ induced Inflammatory Cell death characterized by Inflammatory Cell death, PANoptosis. Mechanistically, TNF-α and IFN-γ co-treatment activated the JAK/STAT1/IRF1 axis, inducing nitric oxide production and driving caspase-8/FADD-mediated PANoptosis. TNF-α and IFN-γ caused a lethal cytokine shock in mice that mirrors the tissue damage and inflammation of COVID-19, and inhibiting PANoptosis protected mice from this pathology and death. Furthermore, treating with neutralizing antibodies against TNF-α and IFN-γ protected mice from mortality during SARS-CoV-2 infection, sepsis, hemophagocytic lymphohistiocytosis, and cytokine shock. Collectively, our findings suggest that blocking the cytokine-mediated Inflammatory Cell death signaling pathway identified here may benefit patients with COVID-19 or other infectious and autoInflammatory diseases by limiting tissue damage/inflammation.
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synergism of tnf α and ifn γ triggers Inflammatory Cell death tissue damage and mortality in sars cov 2 infection and cytokine shock syndromes
bioRxiv, 2020Co-Authors: Rajendra Karki, Min Zheng, Evan P Williams, Balaji Banoth, Bhesh Raj Sharma, Shraddha Tuladhar, Lillian Zalduondo, Parimal Samir, Balamurugan Sundaram, R Subbarao K MalireddiAbstract:The COVID-19 pandemic has caused significant morbidity and mortality. Currently, there is a critical shortage of proven treatment options and an urgent need to understand the pathogenesis of multi-organ failure and lung damage. Cytokine storm is associated with severe inflammation and organ damage during COVID-19. However, a detailed molecular pathway defining this cytokine storm is lacking, and gaining mechanistic understanding of how SARS-CoV-2 elicits a hyperactive Inflammatory response is critical to develop effective therapeutics. Of the multiple Inflammatory cytokines produced by innate immune Cells during SARS-CoV-2 infection, we found that the combined production of TNF-α and IFN-γ specifically induced Inflammatory Cell death, PANoptosis, characterized by gasdermin-mediated pyroptosis, caspase-8-mediated apoptosis, and MLKL-mediated necroptosis. Deletion of pyroptosis, apoptosis, or necroptosis mediators individually was not sufficient to protect against Cell death. However, Cells deficient in both RIPK3 and caspase-8 or RIPK3 and FADD were resistant to this Cell death. Mechanistically, the JAK/STAT1/IRF1 axis activated by TNF-α and IFN-γ co-treatment induced iNOS for the production of nitric oxide. Pharmacological and genetic deletion of this pathway inhibited pyroptosis, apoptosis, and necroptosis in macrophages. Moreover, inhibition of PANoptosis protected mice from TNF-α and IFN-γ-induced lethal cytokine shock that mirrors the pathological symptoms of COVID-19. In vivo neutralization of both TNF-α and IFN-γ in multiple disease models associated with cytokine storm showed that this treatment provided substantial protection against not only SARS-CoV-2 infection, but also sepsis, hemophagocytic lymphohistiocytosis, and cytokine shock models, demonstrating the broad physiological relevance of this mechanism. Collectively, our findings suggest that blocking the cytokine-mediated Inflammatory Cell death signaling pathway identified here may benefit patients with COVID-19 or other cytokine storm-driven syndromes by limiting inflammation and tissue damage. The findings also provide a molecular and mechanistic description for the term cytokine storm. Additionally, these results open new avenues for the treatment of other infectious and autoInflammatory diseases and cancers where TNF-α and IFN-γ synergism play key pathological roles.
-
impaired nlrp3 inflammasome activation pyroptosis leads to robust Inflammatory Cell death via caspase 8 ripk3 during coronavirus infection
Journal of Biological Chemistry, 2020Co-Authors: Min Zheng, Richard J. Webby, Rudragouda Channappanavar, Evan P Williams, R Subbarao K Malireddi, Rajendra Karki, Balaji Banoth, Amanda R Burton, Colleen B Jonsson, Thirumaladevi KannegantiAbstract:Coronaviruses have caused several zoonotic infections in the past two decades, leading to significant morbidity and mortality globally. Balanced regulation of Cell death and Inflammatory immune responses is essential to promote protection against coronavirus infection; however, the underlying mechanisms that control these processes remain to be resolved. Here we demonstrate that infection with the murine coronavirus mouse hepatitis virus (MHV) activated the NLRP3 inflammasome and Inflammatory Cell death in the form of PANoptosis. Deleting NLRP3 inflammasome components or the downstream Cell death executioner gasdermin D (GSDMD) led to an initial reduction in Cell death followed by a robust increase in the incidence of caspase-8- and receptor-interacting serine/threonine-protein kinase 3 (RIPK3)-mediated Inflammatory Cell deathafter coronavirus infection. Additionally, loss of GSDMD promoted robust NLRP3 inflammasome activation. Moreover, the amounts of some cytokines released during coronavirus infection were significantly altered in the absence of GSDMD. Altogether, our findings show that Inflammatory Cell death, PANoptosis, is induced by coronavirus infection and that impaired NLRP3 inflammasome function or pyroptosis can lead to negative consequences for the host. These findings may have important implications for studies of coronavirus-induced disease.