Pub Date : 2022-05-01DOI: 10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1207
Y. Wang, V. Kulkarni, J. Pantaleón García, M. Lethier, S. Cusack, S. Evans
{"title":"RIG-I Is a Novel Receptor for CpG Oligodeoxynucleotides","authors":"Y. Wang, V. Kulkarni, J. Pantaleón García, M. Lethier, S. Cusack, S. Evans","doi":"10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1207","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1207","url":null,"abstract":"","PeriodicalId":307658,"journal":{"name":"A28. THE HOST DELIVERS","volume":"6 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133509215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-01DOI: 10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1215
M. A. Torres Acosta, S. Weinberg, K. Helmin, L. Morales-Nebreda, C. P. Reyes Flores, A. M. Joudi, B. D. Singer
{"title":"AMP-Activated Protein Kinase Is Required for Treg Cell Function During Microenvironmental Stress","authors":"M. A. Torres Acosta, S. Weinberg, K. Helmin, L. Morales-Nebreda, C. P. Reyes Flores, A. M. Joudi, B. D. Singer","doi":"10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1215","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1215","url":null,"abstract":"","PeriodicalId":307658,"journal":{"name":"A28. THE HOST DELIVERS","volume":"16 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131422009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-01DOI: 10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1201
V. Kulkarni, Y. Wang, J. Pantaleón García, S. Evans
{"title":"Pam2-ODN Induces Protection Against Acute Bacterial Pneumonia by Redox Based Activation of Lung Epithelial STAT3","authors":"V. Kulkarni, Y. Wang, J. Pantaleón García, S. Evans","doi":"10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1201","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1201","url":null,"abstract":"","PeriodicalId":307658,"journal":{"name":"A28. THE HOST DELIVERS","volume":"54 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131855134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-01DOI: 10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1209
J. Girkin, N.E. Bryant, S. Loo, C. Demaison, F. Mercuri, N. Bartlett
{"title":"TLR2/6 Agonist Treatment Enhances Antiviral Innate Immune Responses in a Novel Mouse Coronavirus Respiratory Infection Model","authors":"J. Girkin, N.E. Bryant, S. Loo, C. Demaison, F. Mercuri, N. Bartlett","doi":"10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1209","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1209","url":null,"abstract":"","PeriodicalId":307658,"journal":{"name":"A28. THE HOST DELIVERS","volume":"28 2 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133593592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-01DOI: 10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1194
J. Pantaléon-García, L.M. Pacheco Hernandez, V. Kulkarni, M. Longmire, Y. Wang, S. Evans
Rationale: The SARS-CoV-2 pandemic has underscored the need for novel anti-infectious strategies, including host-directed therapeutics, against existing and emerging respiratory pathogens. We have reported that an aerosolized therapeutic comprised of a Toll-like receptor (TLR)-2/6 agonist, Pam2CSK4, and a TLR-9 agonist, ODN M362, stimulate pathogen-agnostic innate immune responses in lung epithelial cells. This therapeutic (“Pam2-ODN”) promotes synergistic microbicidal activity and host survival benefit against pneumonia caused by a wide range of pathogens. Here, we study the immunomodulatory signaling mechanisms required to effect this inducible epithelial resistance. Methods: Bioinformatic analysis of transcriptional responses from human and mouse lung epithelium al cells to influenza A H1N1 or SARS-CoV-2 (GSE147507) or Pam2-ODN (GSE289984, GSE26864) were analyzed using R and IPA software to identify essential transcription factors (TFs). Lung cell population dynamics were studied for TFs related to Pam2-ODN immunomodulatory signaling using high-throughput imaging flow cytometry (IFC). Human or mouse lung epithelial cells were stimulated with PBS or Pam2-ODN and single or dual inhibitors of TFs before challeng with influenza A H3N2 (IAV) or coronavirus OC43 (CoV) to compare the epithelium-specific transcriptional control of relevant TFs using in-cell western blotting, IFC and hemagglutination for viral burdens. Results: Functional enrichment analysis revealed RelA and cJUN to be major immunomodulatory TFs of Pam2-ODN and activators of leukocyte- and epithelial-derived antiviral immune mechanisms targeting replication of influenza A and SARS-CoV-2. Cell population dynamics studied from mouse lungs confirmed activation of RelA and cJUN in CD45+, EpCAM- leukocytes and in CD45-, EpCAM+ epithelial cells, with predominant activation of the lung epithelium and none or minimal activation of structural cell populations such as fibroblasts or endothelial cells. Studies of epithelium-specific signaling in vitro revealed co-activation of RelA-(pS536) and cJun- (pS73) TFs with Pam2-ODN, and earlier onset of cJUN phosphorylation and nuclear translocation with Pam2-ODN after IAV or CoV infection. Individual or dual inhibition of RelA and/or cJUN activity in vitro disrupted the antiviral activity of Pam2-ODN of IAV infected cells. Conclusion: Pam2-ODN induces unique, pathogen-agnostic protective signaling in lung epithelial cells that involves cooperative activation of RelA and cJUN. This combined TF signaling mechanism is not observed in other structural lung cell populations after Pam2-ODN exposure. Further, the phospho-regulation dynamics of RelA and cJUN are not replicated by IAV or CoV infection alone, suggesting a novel therapeutic process that can be leveraged to protect individuals against pneumonia. (Figure Presented).
{"title":"Inducible Resistance Against Viral Pneumonia Requires a Lung Epithelium-Specific Transcriptional Interaction Between RelA and cJUN","authors":"J. Pantaléon-García, L.M. Pacheco Hernandez, V. Kulkarni, M. Longmire, Y. Wang, S. Evans","doi":"10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1194","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1194","url":null,"abstract":"Rationale: The SARS-CoV-2 pandemic has underscored the need for novel anti-infectious strategies, including host-directed therapeutics, against existing and emerging respiratory pathogens. We have reported that an aerosolized therapeutic comprised of a Toll-like receptor (TLR)-2/6 agonist, Pam2CSK4, and a TLR-9 agonist, ODN M362, stimulate pathogen-agnostic innate immune responses in lung epithelial cells. This therapeutic (“Pam2-ODN”) promotes synergistic microbicidal activity and host survival benefit against pneumonia caused by a wide range of pathogens. Here, we study the immunomodulatory signaling mechanisms required to effect this inducible epithelial resistance. Methods: Bioinformatic analysis of transcriptional responses from human and mouse lung epithelium al cells to influenza A H1N1 or SARS-CoV-2 (GSE147507) or Pam2-ODN (GSE289984, GSE26864) were analyzed using R and IPA software to identify essential transcription factors (TFs). Lung cell population dynamics were studied for TFs related to Pam2-ODN immunomodulatory signaling using high-throughput imaging flow cytometry (IFC). Human or mouse lung epithelial cells were stimulated with PBS or Pam2-ODN and single or dual inhibitors of TFs before challeng with influenza A H3N2 (IAV) or coronavirus OC43 (CoV) to compare the epithelium-specific transcriptional control of relevant TFs using in-cell western blotting, IFC and hemagglutination for viral burdens. Results: Functional enrichment analysis revealed RelA and cJUN to be major immunomodulatory TFs of Pam2-ODN and activators of leukocyte- and epithelial-derived antiviral immune mechanisms targeting replication of influenza A and SARS-CoV-2. Cell population dynamics studied from mouse lungs confirmed activation of RelA and cJUN in CD45+, EpCAM- leukocytes and in CD45-, EpCAM+ epithelial cells, with predominant activation of the lung epithelium and none or minimal activation of structural cell populations such as fibroblasts or endothelial cells. Studies of epithelium-specific signaling in vitro revealed co-activation of RelA-(pS536) and cJun- (pS73) TFs with Pam2-ODN, and earlier onset of cJUN phosphorylation and nuclear translocation with Pam2-ODN after IAV or CoV infection. Individual or dual inhibition of RelA and/or cJUN activity in vitro disrupted the antiviral activity of Pam2-ODN of IAV infected cells. Conclusion: Pam2-ODN induces unique, pathogen-agnostic protective signaling in lung epithelial cells that involves cooperative activation of RelA and cJUN. This combined TF signaling mechanism is not observed in other structural lung cell populations after Pam2-ODN exposure. Further, the phospho-regulation dynamics of RelA and cJUN are not replicated by IAV or CoV infection alone, suggesting a novel therapeutic process that can be leveraged to protect individuals against pneumonia. (Figure Presented).","PeriodicalId":307658,"journal":{"name":"A28. THE HOST DELIVERS","volume":"65 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134087951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-01DOI: 10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1211
M. El Sheikh, I. Angers, S. Qureshi
{"title":"Genetic Regulation of the Host Immune Response to Cryptococcus Neoformans Infection","authors":"M. El Sheikh, I. Angers, S. Qureshi","doi":"10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1211","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1211","url":null,"abstract":"","PeriodicalId":307658,"journal":{"name":"A28. THE HOST DELIVERS","volume":"3 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133891064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-01DOI: 10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1210
K. Park, I. Advani, J.A. Masso Silva, J. Pham, L. C. Crotty Alexander
{"title":"The Effects of E-cigarette Use, Cigarette Smoke and Dual-Use of Both on Murine Susceptibility to Streptococcal Pneumonia","authors":"K. Park, I. Advani, J.A. Masso Silva, J. Pham, L. C. Crotty Alexander","doi":"10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1210","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1210","url":null,"abstract":"","PeriodicalId":307658,"journal":{"name":"A28. THE HOST DELIVERS","volume":"46 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128884272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-01DOI: 10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1195
L. M. Rich, E. Vanderwall, K. Barrow, M. White, D. Jackson, M. Altman, J. Debley
{"title":"Bronchial Epithelial ACE-2 and SARS-CoV-2 Replication in Asthmatic and Healthy Children","authors":"L. M. Rich, E. Vanderwall, K. Barrow, M. White, D. Jackson, M. Altman, J. Debley","doi":"10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1195","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1195","url":null,"abstract":"","PeriodicalId":307658,"journal":{"name":"A28. THE HOST DELIVERS","volume":"7 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115009526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-01DOI: 10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1200
M. Maishan, H. Taenaka, S. Matsumoto, X. Fang, S. Sridhar, R. Lucas, M. Matthay
{"title":"Targeted Activation of the Apical Epithelial Sodium Channel Alpha Subunit Preserves Alveolar Fluid Clearance in Bacterial Pneumonia (S. pneumoniae) in the Ex Vivo Perfused Human Lung","authors":"M. Maishan, H. Taenaka, S. Matsumoto, X. Fang, S. Sridhar, R. Lucas, M. Matthay","doi":"10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1200","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1200","url":null,"abstract":"","PeriodicalId":307658,"journal":{"name":"A28. THE HOST DELIVERS","volume":"38 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129905388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-01DOI: 10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1216
C. Langouet-Astrie, K. Oshima, S. McMurty, Y. Yang, J. Kwiecinski, J. Liu, A. Horswill, E. Schmidt
{"title":"The Influenza-Injured Lung Microenvironment Promotes Methicillin-Resistant Staphylococcus Aureus (MRSA) Virulence, Leading to Secondary Pneumonia","authors":"C. Langouet-Astrie, K. Oshima, S. McMurty, Y. Yang, J. Kwiecinski, J. Liu, A. Horswill, E. Schmidt","doi":"10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1216","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1216","url":null,"abstract":"","PeriodicalId":307658,"journal":{"name":"A28. THE HOST DELIVERS","volume":"14 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132197111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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