Enhanced resistance to Listeria infection in mice surviving sepsis: the role of lipid metabolism and myeloid cell reprogramming
IntroductionImmune resilience is the capacity of the immune system to recover from sepsis-induced organ injury and reestablish host defense. While sepsis survivors are often viewed as immunocompromised, recent studies suggest that some may acquire adaptive immune traits that enhance resistance to se...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-05-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1588987/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850122458476052480 |
|---|---|
| author | Haruki Watanabe Tengfei Song Jaewoo Choi Moses Lee Kwangmin Choi Junhwan Kim Junhwan Kim Barbara Sherry Barbara Sherry Betty Diamond Betty Diamond Yong-Rui Zou Yong-Rui Zou Myoungsun Son Myoungsun Son |
| author_facet | Haruki Watanabe Tengfei Song Jaewoo Choi Moses Lee Kwangmin Choi Junhwan Kim Junhwan Kim Barbara Sherry Barbara Sherry Betty Diamond Betty Diamond Yong-Rui Zou Yong-Rui Zou Myoungsun Son Myoungsun Son |
| author_sort | Haruki Watanabe |
| collection | DOAJ |
| description | IntroductionImmune resilience is the capacity of the immune system to recover from sepsis-induced organ injury and reestablish host defense. While sepsis survivors are often viewed as immunocompromised, recent studies suggest that some may acquire adaptive immune traits that enhance resistance to secondary infections.MethodsWe employed a murine cecal ligation and puncture (CLP) model to study polymicrobial sepsis and subsequent immune responses. Listeria monocytogenes was used as a model intracellular pathogen to assess immune protection. We analyzed myeloid cell phenotypes using single-cell RNA sequencing and evaluated lipid metabolic changes through quantitative RT-PCR, immunohistochemistry, serum cytokine assays, and plasma lipidomics.ResultsSepsis-surviving mice showed enhanced resistance to Listeria infection. Single-cell RNA sequencing revealed transcriptional reprogramming in splenic CD11b+Ly6Chigh myeloid cells, including downregulation of lipoprotein lipase and lipid efflux genes. CD11b+ myeloid cells exhibited increased lipid droplet accumulation, accompanied by elevated serum interferon-gamma (IFN-γ) levels. Plasma lipidomics identified systemic lipid remodeling, with increased phosphatidylserine and decreased phosphatidylinositol and phosphatidylglycerol levels.DiscussionOur findings suggest that sepsis survival induces lipid metabolic reprogramming in myeloid cells, contributing to enhanced immunity against intracellular pathogens. These insights reveal potential therapeutic targets within lipid metabolic pathways to improve host defense in sepsis survivors. |
| format | Article |
| id | doaj-art-305def4ac5ce43d3b3d468c4c07414be |
| institution | OA Journals |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-305def4ac5ce43d3b3d468c4c07414be2025-08-20T02:34:50ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-05-011610.3389/fphar.2025.15889871588987Enhanced resistance to Listeria infection in mice surviving sepsis: the role of lipid metabolism and myeloid cell reprogrammingHaruki Watanabe0Tengfei Song1Jaewoo Choi2Moses Lee3Kwangmin Choi4Junhwan Kim5Junhwan Kim6Barbara Sherry7Barbara Sherry8Betty Diamond9Betty Diamond10Yong-Rui Zou11Yong-Rui Zou12Myoungsun Son13Myoungsun Son14Institute of Molecular Medicine, Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, United StatesInstitute of Molecular Medicine, Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, United StatesDepartment of Chemistry, Oregon State University, Corvallis, OR, United StatesInstitute of Molecular Medicine, Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, United StatesDivision of Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United StatesInstitute of Bioelectronic Medicine, Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, United StatesDepartment of Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, United StatesInstitute of Molecular Medicine, Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, United StatesDepartment of Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, United StatesInstitute of Molecular Medicine, Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, United StatesDepartment of Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, United StatesInstitute of Molecular Medicine, Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, United StatesDepartment of Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, United StatesInstitute of Molecular Medicine, Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, United StatesDepartment of Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, United StatesIntroductionImmune resilience is the capacity of the immune system to recover from sepsis-induced organ injury and reestablish host defense. While sepsis survivors are often viewed as immunocompromised, recent studies suggest that some may acquire adaptive immune traits that enhance resistance to secondary infections.MethodsWe employed a murine cecal ligation and puncture (CLP) model to study polymicrobial sepsis and subsequent immune responses. Listeria monocytogenes was used as a model intracellular pathogen to assess immune protection. We analyzed myeloid cell phenotypes using single-cell RNA sequencing and evaluated lipid metabolic changes through quantitative RT-PCR, immunohistochemistry, serum cytokine assays, and plasma lipidomics.ResultsSepsis-surviving mice showed enhanced resistance to Listeria infection. Single-cell RNA sequencing revealed transcriptional reprogramming in splenic CD11b+Ly6Chigh myeloid cells, including downregulation of lipoprotein lipase and lipid efflux genes. CD11b+ myeloid cells exhibited increased lipid droplet accumulation, accompanied by elevated serum interferon-gamma (IFN-γ) levels. Plasma lipidomics identified systemic lipid remodeling, with increased phosphatidylserine and decreased phosphatidylinositol and phosphatidylglycerol levels.DiscussionOur findings suggest that sepsis survival induces lipid metabolic reprogramming in myeloid cells, contributing to enhanced immunity against intracellular pathogens. These insights reveal potential therapeutic targets within lipid metabolic pathways to improve host defense in sepsis survivors.https://www.frontiersin.org/articles/10.3389/fphar.2025.1588987/fullsepsisListeria monocytogeneslipid metabolismlipid dropletssingle-cell RNA sequencingmyeloid cells |
| spellingShingle | Haruki Watanabe Tengfei Song Jaewoo Choi Moses Lee Kwangmin Choi Junhwan Kim Junhwan Kim Barbara Sherry Barbara Sherry Betty Diamond Betty Diamond Yong-Rui Zou Yong-Rui Zou Myoungsun Son Myoungsun Son Enhanced resistance to Listeria infection in mice surviving sepsis: the role of lipid metabolism and myeloid cell reprogramming Frontiers in Pharmacology sepsis Listeria monocytogenes lipid metabolism lipid droplets single-cell RNA sequencing myeloid cells |
| title | Enhanced resistance to Listeria infection in mice surviving sepsis: the role of lipid metabolism and myeloid cell reprogramming |
| title_full | Enhanced resistance to Listeria infection in mice surviving sepsis: the role of lipid metabolism and myeloid cell reprogramming |
| title_fullStr | Enhanced resistance to Listeria infection in mice surviving sepsis: the role of lipid metabolism and myeloid cell reprogramming |
| title_full_unstemmed | Enhanced resistance to Listeria infection in mice surviving sepsis: the role of lipid metabolism and myeloid cell reprogramming |
| title_short | Enhanced resistance to Listeria infection in mice surviving sepsis: the role of lipid metabolism and myeloid cell reprogramming |
| title_sort | enhanced resistance to listeria infection in mice surviving sepsis the role of lipid metabolism and myeloid cell reprogramming |
| topic | sepsis Listeria monocytogenes lipid metabolism lipid droplets single-cell RNA sequencing myeloid cells |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1588987/full |
| work_keys_str_mv | AT harukiwatanabe enhancedresistancetolisteriainfectioninmicesurvivingsepsistheroleoflipidmetabolismandmyeloidcellreprogramming AT tengfeisong enhancedresistancetolisteriainfectioninmicesurvivingsepsistheroleoflipidmetabolismandmyeloidcellreprogramming AT jaewoochoi enhancedresistancetolisteriainfectioninmicesurvivingsepsistheroleoflipidmetabolismandmyeloidcellreprogramming AT moseslee enhancedresistancetolisteriainfectioninmicesurvivingsepsistheroleoflipidmetabolismandmyeloidcellreprogramming AT kwangminchoi enhancedresistancetolisteriainfectioninmicesurvivingsepsistheroleoflipidmetabolismandmyeloidcellreprogramming AT junhwankim enhancedresistancetolisteriainfectioninmicesurvivingsepsistheroleoflipidmetabolismandmyeloidcellreprogramming AT junhwankim enhancedresistancetolisteriainfectioninmicesurvivingsepsistheroleoflipidmetabolismandmyeloidcellreprogramming AT barbarasherry enhancedresistancetolisteriainfectioninmicesurvivingsepsistheroleoflipidmetabolismandmyeloidcellreprogramming AT barbarasherry enhancedresistancetolisteriainfectioninmicesurvivingsepsistheroleoflipidmetabolismandmyeloidcellreprogramming AT bettydiamond enhancedresistancetolisteriainfectioninmicesurvivingsepsistheroleoflipidmetabolismandmyeloidcellreprogramming AT bettydiamond enhancedresistancetolisteriainfectioninmicesurvivingsepsistheroleoflipidmetabolismandmyeloidcellreprogramming AT yongruizou enhancedresistancetolisteriainfectioninmicesurvivingsepsistheroleoflipidmetabolismandmyeloidcellreprogramming AT yongruizou enhancedresistancetolisteriainfectioninmicesurvivingsepsistheroleoflipidmetabolismandmyeloidcellreprogramming AT myoungsunson enhancedresistancetolisteriainfectioninmicesurvivingsepsistheroleoflipidmetabolismandmyeloidcellreprogramming AT myoungsunson enhancedresistancetolisteriainfectioninmicesurvivingsepsistheroleoflipidmetabolismandmyeloidcellreprogramming |