Leukocyte‐Derived High‐Mobility Group Box 1 Governs Hepatic Immune Responses to Listeria monocytogenes
High‐mobility group box 1 (HMGB1) is a nucleoprotein with proinflammatory functions following cellular release during tissue damage. Moreover, antibody‐mediated HMGB1 neutralization alleviates lipopolysaccharide (LPS)‐induced shock, suggesting a role for HMGB1 as a superordinate therapeutic target f...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wolters Kluwer Health/LWW
2021-12-01
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| Series: | Hepatology Communications |
| Online Access: | https://doi.org/10.1002/hep4.1777 |
| _version_ | 1828044099191570432 |
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| author | Annika Volmari Katharina Foelsch Elisabeth Zierz Karsten Yan Minyue Qi Karlotta Bartels Stephanie Kondratowicz Marius Boettcher Daniel Reimers Masahiro Nishibori Keyue Liu Robert F. Schwabe Ansgar W. Lohse Samuel Huber Hans‐Willi Mittruecker Peter Huebener |
| author_facet | Annika Volmari Katharina Foelsch Elisabeth Zierz Karsten Yan Minyue Qi Karlotta Bartels Stephanie Kondratowicz Marius Boettcher Daniel Reimers Masahiro Nishibori Keyue Liu Robert F. Schwabe Ansgar W. Lohse Samuel Huber Hans‐Willi Mittruecker Peter Huebener |
| author_sort | Annika Volmari |
| collection | DOAJ |
| description | High‐mobility group box 1 (HMGB1) is a nucleoprotein with proinflammatory functions following cellular release during tissue damage. Moreover, antibody‐mediated HMGB1 neutralization alleviates lipopolysaccharide (LPS)‐induced shock, suggesting a role for HMGB1 as a superordinate therapeutic target for inflammatory and infectious diseases. Recent genetic studies have indicated cell‐intrinsic functions of HMGB1 in phagocytes as critical elements of immune responses to infections, yet the role of extracellular HMGB1 signaling in this context remains elusive. We performed antibody‐mediated and genetic HMGB1 deletion studies accompanied by in vitro experiments to discern context‐dependent cellular sources and functions of extracellular HMGB1 during murine bloodstream infection with Listeria monocytogenes. Antibody‐mediated neutralization of extracellular HMGB1 favors bacterial dissemination and hepatic inflammation in mice. Hepatocyte HMGB1, a key driver of postnecrotic inflammation in the liver, does not affect Listeria‐induced inflammation or mortality. While we confirm that leukocyte HMGB1 deficiency effectuates disseminated listeriosis, we observed no evidence of dysfunctional autophagy, xenophagy, intracellular bacterial degradation, or inflammatory gene induction in primary HMGB1‐deficient phagocytes or altered immune responses to LPS administration. Instead, we demonstrate that mice devoid of leukocyte HMGB1 exhibit impaired hepatic recruitment of inflammatory monocytes early during listeriosis, resulting in alterations of the transcriptional hepatic immune response and insufficient control of bacterial dissemination. Bone marrow chimera indicate that HMGB1 from both liver‐resident and circulating immune cells contributes to effective pathogen control. Conclusion: Leukocyte‐derived extracellular HMGB1 is a critical cofactor in the immunologic control of bloodstream listeriosis. HMGB1 neutralization strategies preclude an efficient host immune response against Listeria. |
| first_indexed | 2024-04-10T17:51:20Z |
| format | Article |
| id | doaj.art-e8ddfffaf1494235a97e00fc6451d930 |
| institution | Directory Open Access Journal |
| issn | 2471-254X |
| language | English |
| last_indexed | 2024-04-10T17:51:20Z |
| publishDate | 2021-12-01 |
| publisher | Wolters Kluwer Health/LWW |
| record_format | Article |
| series | Hepatology Communications |
| spelling | doaj.art-e8ddfffaf1494235a97e00fc6451d9302023-02-02T21:36:01ZengWolters Kluwer Health/LWWHepatology Communications2471-254X2021-12-015122104212010.1002/hep4.1777Leukocyte‐Derived High‐Mobility Group Box 1 Governs Hepatic Immune Responses to Listeria monocytogenesAnnika Volmari0Katharina Foelsch1Elisabeth Zierz2Karsten Yan3Minyue Qi4Karlotta Bartels5Stephanie Kondratowicz6Marius Boettcher7Daniel Reimers8Masahiro Nishibori9Keyue Liu10Robert F. Schwabe11Ansgar W. Lohse12Samuel Huber13Hans‐Willi Mittruecker14Peter Huebener15First Department of Medicine University Medical Center Hamburg‐Eppendorf Hamburg GermanyFirst Department of Medicine University Medical Center Hamburg‐Eppendorf Hamburg GermanyFirst Department of Medicine University Medical Center Hamburg‐Eppendorf Hamburg GermanyInstitute for Immunology University Medical Center Hamburg‐Eppendorf Hamburg GermanyBioinformatics Core Facility University Medical Center Hamburg‐Eppendorf Hamburg GermanyFirst Department of Medicine University Medical Center Hamburg‐Eppendorf Hamburg GermanyFirst Department of Medicine University Medical Center Hamburg‐Eppendorf Hamburg GermanyFirst Department of Medicine University Medical Center Hamburg‐Eppendorf Hamburg GermanyInstitute for Immunology University Medical Center Hamburg‐Eppendorf Hamburg GermanyDepartment of Pharmacology Okayama University Graduate School of MedicineDentistry, and Pharmaceutical Sciences Okayama JapanDepartment of Pharmacology Okayama University Graduate School of MedicineDentistry, and Pharmaceutical Sciences Okayama JapanDepartment of Medicine Columbia University New York NY USAFirst Department of Medicine University Medical Center Hamburg‐Eppendorf Hamburg GermanyFirst Department of Medicine University Medical Center Hamburg‐Eppendorf Hamburg GermanyInstitute for Immunology University Medical Center Hamburg‐Eppendorf Hamburg GermanyFirst Department of Medicine University Medical Center Hamburg‐Eppendorf Hamburg GermanyHigh‐mobility group box 1 (HMGB1) is a nucleoprotein with proinflammatory functions following cellular release during tissue damage. Moreover, antibody‐mediated HMGB1 neutralization alleviates lipopolysaccharide (LPS)‐induced shock, suggesting a role for HMGB1 as a superordinate therapeutic target for inflammatory and infectious diseases. Recent genetic studies have indicated cell‐intrinsic functions of HMGB1 in phagocytes as critical elements of immune responses to infections, yet the role of extracellular HMGB1 signaling in this context remains elusive. We performed antibody‐mediated and genetic HMGB1 deletion studies accompanied by in vitro experiments to discern context‐dependent cellular sources and functions of extracellular HMGB1 during murine bloodstream infection with Listeria monocytogenes. Antibody‐mediated neutralization of extracellular HMGB1 favors bacterial dissemination and hepatic inflammation in mice. Hepatocyte HMGB1, a key driver of postnecrotic inflammation in the liver, does not affect Listeria‐induced inflammation or mortality. While we confirm that leukocyte HMGB1 deficiency effectuates disseminated listeriosis, we observed no evidence of dysfunctional autophagy, xenophagy, intracellular bacterial degradation, or inflammatory gene induction in primary HMGB1‐deficient phagocytes or altered immune responses to LPS administration. Instead, we demonstrate that mice devoid of leukocyte HMGB1 exhibit impaired hepatic recruitment of inflammatory monocytes early during listeriosis, resulting in alterations of the transcriptional hepatic immune response and insufficient control of bacterial dissemination. Bone marrow chimera indicate that HMGB1 from both liver‐resident and circulating immune cells contributes to effective pathogen control. Conclusion: Leukocyte‐derived extracellular HMGB1 is a critical cofactor in the immunologic control of bloodstream listeriosis. HMGB1 neutralization strategies preclude an efficient host immune response against Listeria.https://doi.org/10.1002/hep4.1777 |
| spellingShingle | Annika Volmari Katharina Foelsch Elisabeth Zierz Karsten Yan Minyue Qi Karlotta Bartels Stephanie Kondratowicz Marius Boettcher Daniel Reimers Masahiro Nishibori Keyue Liu Robert F. Schwabe Ansgar W. Lohse Samuel Huber Hans‐Willi Mittruecker Peter Huebener Leukocyte‐Derived High‐Mobility Group Box 1 Governs Hepatic Immune Responses to Listeria monocytogenes Hepatology Communications |
| title | Leukocyte‐Derived High‐Mobility Group Box 1 Governs Hepatic Immune Responses to Listeria monocytogenes |
| title_full | Leukocyte‐Derived High‐Mobility Group Box 1 Governs Hepatic Immune Responses to Listeria monocytogenes |
| title_fullStr | Leukocyte‐Derived High‐Mobility Group Box 1 Governs Hepatic Immune Responses to Listeria monocytogenes |
| title_full_unstemmed | Leukocyte‐Derived High‐Mobility Group Box 1 Governs Hepatic Immune Responses to Listeria monocytogenes |
| title_short | Leukocyte‐Derived High‐Mobility Group Box 1 Governs Hepatic Immune Responses to Listeria monocytogenes |
| title_sort | leukocyte derived high mobility group box 1 governs hepatic immune responses to listeria monocytogenes |
| url | https://doi.org/10.1002/hep4.1777 |
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