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...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	Diseases of the digestive system. Gastroenterology RC799-869
Acceso en línea:	https://doaj.org/article/e8ddfffaf1494235a97e00fc6451d930
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spelling	oai:doaj.org-article:e8ddfffaf1494235a97e00fc6451d9302021-11-30T13:39:17ZLeukocyte‐Derived High‐Mobility Group Box 1 Governs Hepatic Immune Responses to Listeria monocytogenes2471-254X10.1002/hep4.1777https://doaj.org/article/e8ddfffaf1494235a97e00fc6451d9302021-12-01T00:00:00Zhttps://doi.org/10.1002/hep4.1777https://doaj.org/toc/2471-254XHigh‐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.Annika VolmariKatharina FoelschElisabeth ZierzKarsten YanMinyue QiKarlotta BartelsStephanie KondratowiczMarius BoettcherDaniel ReimersMasahiro NishiboriKeyue LiuRobert F. SchwabeAnsgar W. LohseSamuel HuberHans‐Willi MittrueckerPeter HuebenerWileyarticleDiseases of the digestive system. GastroenterologyRC799-869ENHepatology Communications, Vol 5, Iss 12, Pp 2104-2120 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Diseases of the digestive system. Gastroenterology RC799-869
spellingShingle	Diseases of the digestive system. Gastroenterology RC799-869 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
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.
format	article
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
title	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_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_sort	leukocyte‐derived high‐mobility group box 1 governs hepatic immune responses to listeria monocytogenes
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/e8ddfffaf1494235a97e00fc6451d930
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Leukocyte‐Derived High‐Mobility Group Box 1 Governs Hepatic Immune Responses to Listeria monocytogenes

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