PMID- 33776992 OWN - NLM STAT- MEDLINE DCOM- 20210623 LR - 20210623 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 12 DP - 2021 TI - Tenascin-C Deficiency Is Associated With Reduced Bacterial Outgrowth During Klebsiella pneumoniae-Evoked Pneumosepsis in Mice. PG - 600979 LID - 10.3389/fimmu.2021.600979 [doi] LID - 600979 AB - Tenascin C (TNC) is an extracellular matrix glycoprotein that recently emerged as an immunomodulator. TNC-deficient (TNC(-/-)) mice were reported to have a reduced inflammatory response upon systemic administration of lipopolysaccharide, the toxic component of gram-negative bacteria. Here, we investigated the role of TNC during gram-negative pneumonia derived sepsis. TNC(+/+) and TNC(-/-) mice were infected with Klebsiella pneumoniae via the airways and sacrificed 24 and 42 h thereafter for further analysis. Pulmonary TNC protein levels were elevated 42 h after infection in TNC(+/+) mice and remained undetectable in TNC(-/-) mice. TNC(-/-) mice showed modestly lower bacterial loads in lungs and blood, and a somewhat reduced local-but not systemic-inflammatory response. Moreover, TNC(-/-) and TNC(+/+) mice did not differ with regard to neutrophil recruitment, lung pathology or plasma markers of distal organ injury. These results suggest that while TNC shapes the immune response during lipopolysaccharide-induced inflammation, this role may be superseded during pneumosepsis caused by a common gram-negative pathogen. CI - Copyright (c) 2021 Meijer, de Vos, Scicluna, Roelofs, Abou Faycal, Orend, Uhel and van der Poll. FAU - Meijer, Mariska T AU - Meijer MT AD - Center for Experimental and Molecular Medicine, Amsterdam University Medical Centers, Location Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands. AD - Amsterdam Institute for Infection and Immunity, Amsterdam University Medical Centers, Amsterdam, Netherlands. FAU - de Vos, Alex F AU - de Vos AF AD - Center for Experimental and Molecular Medicine, Amsterdam University Medical Centers, Location Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands. AD - Amsterdam Institute for Infection and Immunity, Amsterdam University Medical Centers, Amsterdam, Netherlands. FAU - Scicluna, Brendon P AU - Scicluna BP AD - Center for Experimental and Molecular Medicine, Amsterdam University Medical Centers, Location Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands. AD - Amsterdam Institute for Infection and Immunity, Amsterdam University Medical Centers, Amsterdam, Netherlands. AD - Clinical Epidemiology Biostatistics and Bioinformatics, Amsterdam University Medical Centers, Location Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands. FAU - Roelofs, Joris J AU - Roelofs JJ AD - Department of Pathology, Amsterdam University Medical Centers, Location Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands. FAU - Abou Faycal, Cherine AU - Abou Faycal C AD - The Tumor Microenvironment Laboratory, INSERM UMR_S 1109, Universite Strasbourg, Faculte de Medecine, Hopital Civil, Institut d'Hematologie et d'Immunologie, Federation de Medecine Translationnelle de Strasbourg (FMTS), Strasbourg, France. FAU - Orend, Gertraud AU - Orend G AD - The Tumor Microenvironment Laboratory, INSERM UMR_S 1109, Universite Strasbourg, Faculte de Medecine, Hopital Civil, Institut d'Hematologie et d'Immunologie, Federation de Medecine Translationnelle de Strasbourg (FMTS), Strasbourg, France. FAU - Uhel, Fabrice AU - Uhel F AD - Center for Experimental and Molecular Medicine, Amsterdam University Medical Centers, Location Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands. AD - Amsterdam Institute for Infection and Immunity, Amsterdam University Medical Centers, Amsterdam, Netherlands. FAU - van der Poll, Tom AU - van der Poll T AD - Center for Experimental and Molecular Medicine, Amsterdam University Medical Centers, Location Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands. AD - Amsterdam Institute for Infection and Immunity, Amsterdam University Medical Centers, Amsterdam, Netherlands. AD - Division of Infectious Diseases, Amsterdam University Medical Centers, Location Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210311 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Tenascin) RN - 0 (Tnc protein, mouse) SB - IM MH - Animals MH - Klebsiella Infections/genetics/*immunology/pathology MH - Klebsiella pneumoniae/*immunology MH - Mice MH - Mice, Knockout MH - Pneumonia, Bacterial/genetics/*immunology/pathology MH - Sepsis/genetics/*immunology/pathology MH - Tenascin/*deficiency/immunology PMC - PMC7990887 OTO - NOTNLM OT - Klebsiella pneumoniae (K. pneumoniae) OT - alarmins OT - immune system OT - innate immunity OT - mice OT - pneumonia OT - sepsis OT - tenascin C COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/03/30 06:00 MHDA- 2021/06/24 06:00 PMCR- 2021/01/01 CRDT- 2021/03/29 06:24 PHST- 2020/08/31 00:00 [received] PHST- 2021/02/22 00:00 [accepted] PHST- 2021/03/29 06:24 [entrez] PHST- 2021/03/30 06:00 [pubmed] PHST- 2021/06/24 06:00 [medline] PHST- 2021/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2021.600979 [doi] PST - epublish SO - Front Immunol. 2021 Mar 11;12:600979. doi: 10.3389/fimmu.2021.600979. eCollection 2021.