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Cell Rep
. 2023 Oct 3;42(10):113212.
doi: 10.1016/j.celrep.2023.113212. Online ahead of print. Organ-specific immunity: A tissue analysis framework for investigating local immune responses to SARS-CoV-2
Alphonsus H C Ng 1 , Huiqian Hu 2 , Kai Wang 3 , Kelsey Scherler 3 , Sarah E Warren 4 , Daniel R Zollinger 4 , Jill McKay-Fleisch 4 , Kristina Sorg 4 , Joseph M Beechem 4 , Emily Ragaglia 5 , J Matthew Lacy 6 , Kelly D Smith 7 , Desiree A Marshall 7 , Michael M Bundesmann 8 , Diego López de Castilla 9 , David Corwin 5 , Nicole Yarid 10 , Beatrice S Knudsen 11 , Yue Lu 12 , Jason D Goldman 13 , James R Heath 14
Affiliations
Local immune activation at mucosal surfaces, mediated by mucosal lymphoid tissues, is vital for effective immune responses against pathogens. While pathogens like severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can spread to multiple organs, patients with coronavirus disease 2019 (COVID-19) primarily experience inflammation and damage in their lungs. To investigate this apparent organ-specific immune response, we develop an analytical framework that recognizes the significance of mucosal lymphoid tissues. This framework combines histology, immunofluorescence, spatial transcript profiling, and mathematical modeling to identify cellular and gene expression differences between the lymphoid tissues of the lung and the gut and predict the determinants of those differences. Our findings indicate that mucosal lymphoid tissues are pivotal in organ-specific immune response to SARS-CoV-2, mediating local inflammation and tissue damage and contributing to immune dysfunction. The framework developed here has potential utility in the study of long COVID and may streamline biomarker discovery and treatment design for diseases with differential pathologies at the organ level.
Keywords: COVID-19; CP: Immunology; CP: Microbiology; SARS-CoV-2; biomarker; dendritic cells; digital pathology; local immunity; macrophages; mucosal lymphoid tissues; post-mortem; tissue injury.
. 2023 Oct 3;42(10):113212.
doi: 10.1016/j.celrep.2023.113212. Online ahead of print. Organ-specific immunity: A tissue analysis framework for investigating local immune responses to SARS-CoV-2
Alphonsus H C Ng 1 , Huiqian Hu 2 , Kai Wang 3 , Kelsey Scherler 3 , Sarah E Warren 4 , Daniel R Zollinger 4 , Jill McKay-Fleisch 4 , Kristina Sorg 4 , Joseph M Beechem 4 , Emily Ragaglia 5 , J Matthew Lacy 6 , Kelly D Smith 7 , Desiree A Marshall 7 , Michael M Bundesmann 8 , Diego López de Castilla 9 , David Corwin 5 , Nicole Yarid 10 , Beatrice S Knudsen 11 , Yue Lu 12 , Jason D Goldman 13 , James R Heath 14
Affiliations
- PMID: 37792533
- DOI: 10.1016/j.celrep.2023.113212
Local immune activation at mucosal surfaces, mediated by mucosal lymphoid tissues, is vital for effective immune responses against pathogens. While pathogens like severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can spread to multiple organs, patients with coronavirus disease 2019 (COVID-19) primarily experience inflammation and damage in their lungs. To investigate this apparent organ-specific immune response, we develop an analytical framework that recognizes the significance of mucosal lymphoid tissues. This framework combines histology, immunofluorescence, spatial transcript profiling, and mathematical modeling to identify cellular and gene expression differences between the lymphoid tissues of the lung and the gut and predict the determinants of those differences. Our findings indicate that mucosal lymphoid tissues are pivotal in organ-specific immune response to SARS-CoV-2, mediating local inflammation and tissue damage and contributing to immune dysfunction. The framework developed here has potential utility in the study of long COVID and may streamline biomarker discovery and treatment design for diseases with differential pathologies at the organ level.
Keywords: COVID-19; CP: Immunology; CP: Microbiology; SARS-CoV-2; biomarker; dendritic cells; digital pathology; local immunity; macrophages; mucosal lymphoid tissues; post-mortem; tissue injury.