Long-term survivors of murine sepsis are predisposed to enhanced LPS-induced lung injury and proinflammatory immune reprogramming Article Swipe
Scott J. Denstaedt
,
Angela C. Bustamante
,
Michael W. Newstead
,
Bethany B. Moore
,
Theodore J. Standiford
,
Rachel L. Zemans
,
Benjamin H. Singer
·
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1152/ajplung.00123.2021
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1152/ajplung.00123.2021
Millions of people who survive sepsis each year are rehospitalized and die due to late pulmonary complications. To prevent and treat these complications, biomarkers and molecular mediators must be identified. Persistent immune reprogramming in the form of immunoparalysis and impaired host defense is proposed to mediate late pulmonary complications after sepsis, particularly new pulmonary infections. However, immune reprogramming may also involve enhanced/primed responses to secondary stimuli, although their contribution to long-term sepsis complications remains understudied. We hypothesize that enhanced/primed immune responses in the lungs of sepsis survivors are associated with late pulmonary complications. To this end, we developed a murine sepsis model using cecal ligation and puncture (CLP) followed 3 wk later by administration of intranasal lipopolysaccharide to induce inflammatory lung injury. Mice surviving sepsis exhibit enhanced lung injury with increased alveolar permeability, neutrophil recruitment, and enhanced Ly6C hi monocyte Tnf expression. To determine the mediators of enhanced lung injury, we performed flow cytometry and RNA sequencing of lungs 3 wk after CLP, prior to lipopolysaccharide. Sepsis survivor mice showed expanded Ly6C hi monocytes populations and increased expression of many inflammatory genes. Of these, S100A8/A9 was also elevated in the circulation of human sepsis survivors for months after sepsis, validating our model and identifying S100A8/A9 as a potential biomarker and therapeutic target for long-term pulmonary complications after sepsis. These data provide new insight into the importance of enhanced/primed immune responses in survivors of sepsis and establish a foundation for additional investigation into the mechanisms mediating this response.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1152/ajplung.00123.2021
- OA Status
- green
- Cited By
- 14
- References
- 97
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3173875904
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W3173875904Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1152/ajplung.00123.2021Digital Object Identifier
- Title
-
Long-term survivors of murine sepsis are predisposed to enhanced LPS-induced lung injury and proinflammatory immune reprogrammingWork title
- Type
-
articleOpenAlex work type
- Language
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enPrimary language
- Publication year
-
2021Year of publication
- Publication date
-
2021-06-23Full publication date if available
- Authors
-
Scott J. Denstaedt, Angela C. Bustamante, Michael W. Newstead, Bethany B. Moore, Theodore J. Standiford, Rachel L. Zemans, Benjamin H. SingerList of authors in order
- Landing page
-
https://doi.org/10.1152/ajplung.00123.2021Publisher landing page
- Open access
-
YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
-
https://www.ncbi.nlm.nih.gov/pmc/articles/8410111Direct OA link when available
- Concepts
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Sepsis, Immunology, Medicine, Immune system, Proinflammatory cytokine, Inflammation, Lung, Lipopolysaccharide, Biomarker, Biology, Internal medicine, BiochemistryTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
14Total citation count in OpenAlex
- Citations by year (recent)
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2025: 3, 2024: 5, 2023: 4, 2022: 2Per-year citation counts (last 5 years)
- References (count)
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97Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.recruitment, | 134 |
| abstract_inverted_index.complications | 48, 72, 215 |
| abstract_inverted_index.investigation | 240 |
| abstract_inverted_index.permeability, | 132 |
| abstract_inverted_index.reprogramming | 32, 57 |
| abstract_inverted_index.understudied. | 74 |
| abstract_inverted_index.administration | 113 |
| abstract_inverted_index.complications, | 22 |
| abstract_inverted_index.complications. | 16, 92 |
| abstract_inverted_index.rehospitalized | 9 |
| abstract_inverted_index.enhanced/primed | 61, 78, 227 |
| abstract_inverted_index.immunoparalysis | 37 |
| abstract_inverted_index.lipopolysaccharide | 116 |
| abstract_inverted_index.lipopolysaccharide. | 165 |
| cited_by_percentile_year.max | 98 |
| cited_by_percentile_year.min | 94 |
| corresponding_author_ids | https://openalex.org/A5044128369 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 7 |
| corresponding_institution_ids | https://openalex.org/I27837315 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.8500000238418579 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.84307902 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |