Peptidoglycan Recognition Protein 2 Regulates Neutrophil Recruitment Into the Lungs After Streptococcus pneumoniae Infection

Peptidoglycan (PGN) recognition proteins (PGLYRPs) are a highly conserved group of host defense proteins in insects and mammals that sense bacterial cell wall PGN and act bactericidally or cleave PGN by amidase function. Streptococcus (S.) pneumoniae is one of the top five killers worldwide and caus...

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Main Authors: Alexander N. Dabrowski, Claudia Conrad, Ulrike Behrendt, Anshu Shrivastav, Nelli Baal, Sandra M. Wienhold, Holger Hackstein, Philippe D. N’Guessan, Sahar Aly, Katrin Reppe, Norbert Suttorp, Janine Zahlten
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-02-01
Series:Frontiers in Microbiology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fmicb.2019.00199/full
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author Alexander N. Dabrowski
Claudia Conrad
Ulrike Behrendt
Anshu Shrivastav
Nelli Baal
Sandra M. Wienhold
Sandra M. Wienhold
Holger Hackstein
Philippe D. N’Guessan
Sahar Aly
Katrin Reppe
Katrin Reppe
Norbert Suttorp
Janine Zahlten
spellingShingle Alexander N. Dabrowski
Claudia Conrad
Ulrike Behrendt
Anshu Shrivastav
Nelli Baal
Sandra M. Wienhold
Sandra M. Wienhold
Holger Hackstein
Philippe D. N’Guessan
Sahar Aly
Katrin Reppe
Katrin Reppe
Norbert Suttorp
Janine Zahlten
Peptidoglycan Recognition Protein 2 Regulates Neutrophil Recruitment Into the Lungs After Streptococcus pneumoniae Infection
Frontiers in Microbiology
infectious diseases
innate immunity
mouse
PGRP
PGLYRP2
pneumonia
author_facet Alexander N. Dabrowski
Claudia Conrad
Ulrike Behrendt
Anshu Shrivastav
Nelli Baal
Sandra M. Wienhold
Sandra M. Wienhold
Holger Hackstein
Philippe D. N’Guessan
Sahar Aly
Katrin Reppe
Katrin Reppe
Norbert Suttorp
Janine Zahlten
author_sort Alexander N. Dabrowski
title Peptidoglycan Recognition Protein 2 Regulates Neutrophil Recruitment Into the Lungs After Streptococcus pneumoniae Infection
title_short Peptidoglycan Recognition Protein 2 Regulates Neutrophil Recruitment Into the Lungs After Streptococcus pneumoniae Infection
title_full Peptidoglycan Recognition Protein 2 Regulates Neutrophil Recruitment Into the Lungs After Streptococcus pneumoniae Infection
title_fullStr Peptidoglycan Recognition Protein 2 Regulates Neutrophil Recruitment Into the Lungs After Streptococcus pneumoniae Infection
title_full_unstemmed Peptidoglycan Recognition Protein 2 Regulates Neutrophil Recruitment Into the Lungs After Streptococcus pneumoniae Infection
title_sort peptidoglycan recognition protein 2 regulates neutrophil recruitment into the lungs after streptococcus pneumoniae infection
publisher Frontiers Media S.A.
series Frontiers in Microbiology
issn 1664-302X
publishDate 2019-02-01
description Peptidoglycan (PGN) recognition proteins (PGLYRPs) are a highly conserved group of host defense proteins in insects and mammals that sense bacterial cell wall PGN and act bactericidally or cleave PGN by amidase function. Streptococcus (S.) pneumoniae is one of the top five killers worldwide and causes, e.g., pneumonia, endocarditis, meningitis and sepsis. S. pneumoniae accounts for approximately 1.5–2 million deaths every year. The risk of antibiotic resistance and a general poor prognosis in young children and elderly people have led to the need for new treatment approaches. To the best of our knowledge, there is no report on the relevance of PGLYRP2 in lung infections. Therefore, we infected mice deficient for PGLYRP2 transnasally with S. pneumoniae and examined the innate immune response in comparison to WT animals. As expected, PGLYRP2-KO animals had to be sacrificed earlier than their WT counterparts, and this was due to higher bacteremia. The higher bacterial load in the PGLYRP2-KO mice was accomplished with lower amounts of proinflammatory cytokines in the lungs. This led to an abolished recruitment of neutrophils into the lungs, the spread of bacteria and the subsequent aggravated course of the disease and early mortality of the PGLYRP2-KO mice. These data suggest a substantial role of PGLYRP2 in the early defense against S. pneumoniae infection, and PGLYRP2 might also affect other infections in the lungs.
topic infectious diseases
innate immunity
mouse
PGRP
PGLYRP2
pneumonia
url https://www.frontiersin.org/article/10.3389/fmicb.2019.00199/full
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spelling doaj-bc090d8862bc4b56ad23f2489735e65b2020-11-24T22:49:37ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2019-02-011010.3389/fmicb.2019.00199425432Peptidoglycan Recognition Protein 2 Regulates Neutrophil Recruitment Into the Lungs After Streptococcus pneumoniae InfectionAlexander N. Dabrowski0Claudia Conrad1Ulrike Behrendt2Anshu Shrivastav3Nelli Baal4Sandra M. Wienhold5Sandra M. Wienhold6Holger Hackstein7Philippe D. N’Guessan8Sahar Aly9Katrin Reppe10Katrin Reppe11Norbert Suttorp12Janine Zahlten13Department of Infectious Diseases and Respiratory Medicine, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, GermanyDepartment of Infectious Diseases and Respiratory Medicine, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, GermanyDepartment of Infectious Diseases and Respiratory Medicine, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, GermanyDepartment of Infectious Diseases and Respiratory Medicine, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, GermanyImmunology and Transfusion Medicine, Justus Liebig University Giessen, Giessen, GermanyDepartment of Infectious Diseases and Respiratory Medicine, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, GermanyDivision of Pulmonary Inflammation, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, GermanyImmunology and Transfusion Medicine, Justus Liebig University Giessen, Giessen, GermanyDepartment of Infectious Diseases and Respiratory Medicine, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, GermanyDepartment of Infectious Diseases and Respiratory Medicine, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, GermanyDepartment of Infectious Diseases and Respiratory Medicine, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, GermanyDivision of Pulmonary Inflammation, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, GermanyDepartment of Infectious Diseases and Respiratory Medicine, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, GermanyDepartment of Infectious Diseases and Respiratory Medicine, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, GermanyPeptidoglycan (PGN) recognition proteins (PGLYRPs) are a highly conserved group of host defense proteins in insects and mammals that sense bacterial cell wall PGN and act bactericidally or cleave PGN by amidase function. Streptococcus (S.) pneumoniae is one of the top five killers worldwide and causes, e.g., pneumonia, endocarditis, meningitis and sepsis. S. pneumoniae accounts for approximately 1.5–2 million deaths every year. The risk of antibiotic resistance and a general poor prognosis in young children and elderly people have led to the need for new treatment approaches. To the best of our knowledge, there is no report on the relevance of PGLYRP2 in lung infections. Therefore, we infected mice deficient for PGLYRP2 transnasally with S. pneumoniae and examined the innate immune response in comparison to WT animals. As expected, PGLYRP2-KO animals had to be sacrificed earlier than their WT counterparts, and this was due to higher bacteremia. The higher bacterial load in the PGLYRP2-KO mice was accomplished with lower amounts of proinflammatory cytokines in the lungs. This led to an abolished recruitment of neutrophils into the lungs, the spread of bacteria and the subsequent aggravated course of the disease and early mortality of the PGLYRP2-KO mice. These data suggest a substantial role of PGLYRP2 in the early defense against S. pneumoniae infection, and PGLYRP2 might also affect other infections in the lungs.https://www.frontiersin.org/article/10.3389/fmicb.2019.00199/fullinfectious diseasesinnate immunitymousePGRPPGLYRP2pneumonia