Contribution of Puma to Inflammatory Resolution During Early Pneumococcal Pneumonia
Apoptosis of cells at the site of infection is a requirement for shutdown of inflammatory signaling, avoiding tissue damage, and preventing progression of sepsis. Puma+/+ and Puma-/- mice were challenged with TIGR4 strain pneumococcus and cytokines were quantitated from lungs and blood using a magne...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2022.886901/full |
| _version_ | 1818552371671728128 |
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| author | Daniel E. Kennedy II Perceus Mody Jean-Francois Gout Wei Tan Keun Seok Seo Alicia K. Olivier Jason W. Rosch Justin A. Thornton |
| author_facet | Daniel E. Kennedy II Perceus Mody Jean-Francois Gout Wei Tan Keun Seok Seo Alicia K. Olivier Jason W. Rosch Justin A. Thornton |
| author_sort | Daniel E. Kennedy II |
| collection | DOAJ |
| description | Apoptosis of cells at the site of infection is a requirement for shutdown of inflammatory signaling, avoiding tissue damage, and preventing progression of sepsis. Puma+/+ and Puma-/- mice were challenged with TIGR4 strain pneumococcus and cytokines were quantitated from lungs and blood using a magnetic bead panel analysis. Puma-/- mice exhibited higher lung and blood cytokine levels of several major inflammatory cytokines, including IL-6, G-CSF, RANTES, IL-12, IFN-ϒ, and IP-10. Puma-/- mice were more susceptible to bacterial dissemination and exhibited more weight loss than their wild-type counterparts. RNA sequencing analysis of whole pulmonary tissue revealed Puma-dependent regulation of Nrxn2, Adam19, and Eln. Enrichment of gene ontology groups differentially expressed in Puma-/- tissues were strongly correlated to IFN-β and -ϒ signaling. Here, we demonstrate for the first time the role of Puma in prohibition of the cytokine storm during bacterial pneumonia. These findings further suggest a role for targeting immunomodulation of IFN signaling during pulmonary inflammation. Additionally, our findings suggest previously undemonstrated roles for genes encoding regulatory and binding proteins during the early phase of the innate immune response of pneumococcal pneumonia. |
| first_indexed | 2024-12-12T09:12:20Z |
| format | Article |
| id | doaj.art-393bb0a9aa2c4a2980f87ebaa51cbb8e |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-12-12T09:12:20Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-393bb0a9aa2c4a2980f87ebaa51cbb8e2022-12-22T00:29:29ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882022-05-011210.3389/fcimb.2022.886901886901Contribution of Puma to Inflammatory Resolution During Early Pneumococcal PneumoniaDaniel E. Kennedy II0Perceus Mody1Jean-Francois Gout2Wei Tan3Keun Seok Seo4Alicia K. Olivier5Jason W. Rosch6Justin A. Thornton7Department of Biological Sciences, Mississippi State University, Starkville, MS, United StatesDepartment of Biological Sciences, Mississippi State University, Starkville, MS, United StatesDepartment of Biological Sciences, Mississippi State University, Starkville, MS, United StatesDepartment of Comparative Biomedical Sciences, College of Veterinary Medicine, Mississippi State University, Starkville, MS, United StatesDepartment of Comparative Biomedical Sciences, College of Veterinary Medicine, Mississippi State University, Starkville, MS, United StatesDepartment of Population and Pathobiology, College of Veterinary Medicine, Mississippi State University, Starkville, MS, United StatesDepartment of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN, United StatesDepartment of Biological Sciences, Mississippi State University, Starkville, MS, United StatesApoptosis of cells at the site of infection is a requirement for shutdown of inflammatory signaling, avoiding tissue damage, and preventing progression of sepsis. Puma+/+ and Puma-/- mice were challenged with TIGR4 strain pneumococcus and cytokines were quantitated from lungs and blood using a magnetic bead panel analysis. Puma-/- mice exhibited higher lung and blood cytokine levels of several major inflammatory cytokines, including IL-6, G-CSF, RANTES, IL-12, IFN-ϒ, and IP-10. Puma-/- mice were more susceptible to bacterial dissemination and exhibited more weight loss than their wild-type counterparts. RNA sequencing analysis of whole pulmonary tissue revealed Puma-dependent regulation of Nrxn2, Adam19, and Eln. Enrichment of gene ontology groups differentially expressed in Puma-/- tissues were strongly correlated to IFN-β and -ϒ signaling. Here, we demonstrate for the first time the role of Puma in prohibition of the cytokine storm during bacterial pneumonia. These findings further suggest a role for targeting immunomodulation of IFN signaling during pulmonary inflammation. Additionally, our findings suggest previously undemonstrated roles for genes encoding regulatory and binding proteins during the early phase of the innate immune response of pneumococcal pneumonia.https://www.frontiersin.org/articles/10.3389/fcimb.2022.886901/fullPUMA (p53 upregulated modulator of apoptosis)inflammationstreptococcus pneumoniae (pneumococcus)apoptosisinnate immunity |
| spellingShingle | Daniel E. Kennedy II Perceus Mody Jean-Francois Gout Wei Tan Keun Seok Seo Alicia K. Olivier Jason W. Rosch Justin A. Thornton Contribution of Puma to Inflammatory Resolution During Early Pneumococcal Pneumonia Frontiers in Cellular and Infection Microbiology PUMA (p53 upregulated modulator of apoptosis) inflammation streptococcus pneumoniae (pneumococcus) apoptosis innate immunity |
| title | Contribution of Puma to Inflammatory Resolution During Early Pneumococcal Pneumonia |
| title_full | Contribution of Puma to Inflammatory Resolution During Early Pneumococcal Pneumonia |
| title_fullStr | Contribution of Puma to Inflammatory Resolution During Early Pneumococcal Pneumonia |
| title_full_unstemmed | Contribution of Puma to Inflammatory Resolution During Early Pneumococcal Pneumonia |
| title_short | Contribution of Puma to Inflammatory Resolution During Early Pneumococcal Pneumonia |
| title_sort | contribution of puma to inflammatory resolution during early pneumococcal pneumonia |
| topic | PUMA (p53 upregulated modulator of apoptosis) inflammation streptococcus pneumoniae (pneumococcus) apoptosis innate immunity |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2022.886901/full |
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