Antibiotic treatment-induced secondary IgA deficiency enhances susceptibility to Pseudomonas aeruginosa pneumonia

The Journal of Clinical Investigation
Oliver H RobakBastian Opitz

Abstract

Broad-spectrum antibiotics are widely used with patients in intensive care units (ICUs), many of whom develop hospital-acquired infections with Pseudomonas aeruginosa. Although preceding antimicrobial therapy is known as a major risk factor for P. aeruginosa-induced pneumonia, the underlying mechanisms remain incompletely understood. Here we demonstrate that depletion of the resident microbiota by broad-spectrum antibiotic treatment inhibited TLR-dependent production of a proliferation-inducing ligand (APRIL), resulting in a secondary IgA deficiency in the lung in mice and human ICU patients. Microbiota-dependent local IgA contributed to early antibacterial defense against P. aeruginosa. Consequently, P. aeruginosa-binding IgA purified from lamina propria culture or IgA hybridomas enhanced resistance of antibiotic-treated mice to P. aeruginosa infection after transnasal substitute. Our study provides a mechanistic explanation for the well-documented risk of P. aeruginosa infection following antimicrobial therapy, and we propose local administration of IgA as a novel prophylactic strategy.

References

Jan 1, 1968·International Archives of Allergy and Applied Immunology·P A CrabbéJ F Heremans
Dec 31, 1997·American Journal of Respiratory and Critical Care Medicine·M Garrouste-OrgeasB Schlemmer
Dec 19, 2001·Infection and Immunity·T Dianne LangfordLars Eckmann
Aug 3, 2002·Nature Immunology·Mikhail B LitinskiyAndrea Cerutti
Feb 10, 2004·Proceedings of the National Academy of Sciences of the United States of America·Keiichiro SuzukiSidonia Fagarasan
Aug 6, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Svetlana Shulga-MorskayaMartin L Scott
Sep 10, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Danielle G SouzaMauro M Teixeira
Dec 5, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Markus M HeimesaatOliver Liesenfeld
Jun 28, 2007·PLoS Biology·Chana PalmerPatrick O Brown
Nov 17, 2007·Cell Host & Microbe·Daniel A PetersonJeffrey I Gordon
Dec 3, 2009·JAMA : the Journal of the American Medical Association·Jean-Louis VincentUNKNOWN EPIC II Group of Investigators
Jan 19, 2010·Nature Medicine·Thomas B ClarkeJeffrey N Weiser
Jul 6, 2010·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Ronald N Jones
Sep 18, 2010·Proceedings of the National Academy of Sciences of the United States of America·Les Dethlefsen, David A Relman
Mar 16, 2011·Proceedings of the National Academy of Sciences of the United States of America·Takeshi IchinoheAkiko Iwasaki
Sep 2, 2011·The Journal of Clinical Investigation·Douglas D McCarthyJeffrey L Browning
Nov 2, 2011·Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases·M WoodheadUNKNOWN Joint Taskforce of the European Respiratory Society and European Society for Clinical Microbiology and Infectious Diseases
Sep 15, 2012·Critical Care Medicine·Elaine O PetrofDaren K Heyland
Oct 3, 2012·Current Opinion in Allergy and Clinical Immunology·Ning Wang, Lennart Hammarström
Oct 30, 2012·Nature Reviews. Immunology·Oliver Pabst
Nov 23, 2012·Euro Surveillance : Bulletin Européen Sur Les Maladies Transmissibles = European Communicable Disease Bulletin·P ZarbUNKNOWN Hospital Contact Points for the ECDC pilot point prevalence survey
Jul 17, 2013·American Journal of Respiratory and Critical Care Medicine·Yuichiro ShindoYoshinori Hasegawa
Oct 8, 2013·Nature Reviews. Immunology·Charlie G Buffie, Eric G Pamer
Mar 29, 2014·The New England Journal of Medicine·Shelley S MagillUNKNOWN Emerging Infections Program Healthcare-Associated Infections and Antimicrobial Use Prevalence Survey Team
Oct 26, 2014·The Cochrane Database of Systematic Reviews·Lulong BoXiaoming Deng
Dec 20, 2015·Respirology : Official Journal of the Asian Pacific Society of Respirology·Mark L MeterskyEric M Mortensen
Feb 26, 2016·Journal of Clinical Microbiology·Thomas J GniadekPatricia J Simner
Jul 8, 2016·Nature·Kenya Honda, Dan R Littman

❮ Previous
Next ❯

Citations

Oct 18, 2018·Cellular Microbiology·Alexia DumasOlivier Neyrolles
Apr 12, 2019·Chinese Medical Journal·Sheng Zhang, De-Chang Chen
May 3, 2019·American Journal of Respiratory and Critical Care Medicine·Michael S NiedermanNeil W Schluger
Aug 8, 2019·Current Opinion in Allergy and Clinical Immunology·Roos-Marijn BerbersHelen Louisa Leavis
Sep 5, 2019·Infection and Immunity·Marjolaine Vareille-DelarbreChristiane Forestier
Mar 27, 2019·Viruses·Sandra-Maria WienholdMartin Witzenrath
Mar 7, 2020·Frontiers in Cellular and Infection Microbiology·Raphaël EnaudLaurence Delhaes
May 7, 2019·American Journal of Respiratory Cell and Molecular Biology·Laura MaschirowBastian Opitz
Apr 11, 2019·European Journal of Microbiology & Immunology·Katharina MrazekMarkus M Heimesaat
Oct 31, 2018·Critical Care : the Official Journal of the Critical Care Forum·Sandra-Maria WienholdHolger C Müller-Redetzky
Dec 14, 2018·Nature Microbiology·Josie Libertucci, Vincent B Young
Nov 16, 2018·Frontiers in Physiology·Elizabeth A KennedyMegan T Baldridge
Aug 27, 2019·F1000Research·Burkhard Tümmler
Nov 5, 2019·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Hrishikesh S KulkarniRamsey R Hachem
Jan 31, 2020·Intensive Care Medicine·Nishkantha ArulkumaranAndrew Conway Morris
Jul 17, 2018·The Journal of Clinical Investigation·Juergen LohmeyerSusanne Herold
Oct 21, 2020·Critical Care : the Official Journal of the Critical Care Forum·Rodrigue DesseinEric Kipnis
Nov 12, 2020·Intensive Care Medicine·Charles-Edouard LuytJean-François Timsit
Jan 15, 2021·Science Translational Medicine·Charlotte ThibeaultBastian Opitz
Feb 14, 2021·International Journal of Molecular Sciences·Tsvetelina VelikovaMilena Peruhova
Oct 31, 2020·Frontiers in Immunology·Yongyao YuZhen Xu
Feb 20, 2021·Expert Review of Respiratory Medicine·Bárbara N Porto, Theo J Moraes
Apr 16, 2021·PLoS Pathogens·Giorgia MoriAntje Blumenthal
May 13, 2021·Cell Reports·Derek J PlattJonathan J Miner
Jun 8, 2021·The British Journal of Nutrition·Mona HegazyAhmed Abdelghani
Oct 3, 2021·Biological Chemistry·Maike Willers, Dorothee Viemann

❮ Previous
Next ❯

Methods Mentioned

BETA
ELISA
bronchoalveolar lavage
PCR
lavage
ELISAs
FACS
electrophoresis
flow cytometry

Clinical Trials Mentioned

NCT02912520

Related Concepts

Related Feeds

Antifungals

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Antifungals (ASM)

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Related Papers

Respirology : Official Journal of the Asian Pacific Society of Respirology
Committee for the Japanese Respiratory Society Guidelines in Management of Respiratory
Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia
Radovan UvizlMilan Kolar
© 2022 Meta ULC. All rights reserved