Innate immune response to Streptococcus pyogenes depends on the combined activation of TLR13 and TLR2

PloS One
Christina FieberPavel Kovarik

Abstract

Innate immune recognition of the major human-specific Gram-positive pathogen Streptococcus pyogenes is not understood. Here we show that mice employ Toll-like receptor (TLR) 2- and TLR13-mediated recognition of S. pyogenes. These TLR pathways are non-redundant in the in vivo context of animal infection, but are largely redundant in vitro, as only inactivation of both of them abolishes inflammatory cytokine production by macrophages and dendritic cells infected with S. pyogenes. Mechanistically, S. pyogenes is initially recognized in a phagocytosis-independent manner by TLR2 and subsequently by TLR13 upon internalization. We show that the TLR13 response is specifically triggered by S. pyogenes rRNA and that Tlr13-/- cells respond to S. pyogenes infection solely by engagement of TLR2. TLR13 is absent from humans and, remarkably, we find no equivalent route for S. pyogenes RNA recognition in human macrophages. Phylogenetic analysis reveals that TLR13 occurs in all kingdoms but only in few mammals, including mice and rats, which are naturally resistant against S. pyogenes. Our study establishes that the dissimilar expression of TLR13 in mice and humans has functional consequences for recognition of S. pyogenes in these organisms.

References

Sep 1, 1997·Nucleic Acids Research·S F AltschulD J Lipman
Jun 11, 1999·The Journal of Biological Chemistry·R SchwandnerC J Kirschning
Mar 24, 2004·Nature Reviews. Microbiology·Timothy J Mitchell
Mar 25, 2004·Infection and Immunity·David TorresFrançois Erard
Apr 23, 2004·Infection and Immunity·Oliver GoldmannEva Medina
Sep 18, 2004·Science·Caleb E Finch, Eileen M Crimmins
Nov 6, 2004·Science·Ichiro NakagawaTamotsu Yoshimori
Jan 22, 2005·Nucleic Acids Research·Kazutaka KatohTakashi Miyata
May 10, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kei YasudaHermann Wagner
Oct 29, 2005·The Lancet Infectious Diseases·Jonathan R CarapetisMartin Weber
Jan 20, 2006·Briefings in Functional Genomics & Proteomics·Eva Medina, Andreas Lengeling
Mar 3, 2007·The Journal of Infectious Diseases·David M Morens, Anthony S Fauci
Apr 25, 2007·The Journal of Cell Biology·Melanie M BrinkmannYou-Me Kim
May 26, 2007·Trends in Microbiology·Anne H TartJames M Musser
Apr 9, 2008·Infection and Immunity·Torsten G LoofEva Medina
Aug 20, 2008·Cellular Microbiology·Randall J OlsenJames M Musser
Oct 22, 2008·Proceedings of the National Academy of Sciences of the United States of America·Ioannis GryllosMichael R Wessels
Apr 9, 2009·Proceedings of the National Academy of Sciences of the United States of America·Alexander A NavariniRolf M Zinkernagel
Oct 9, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jürgen HarderGabriel Núñez
Dec 19, 2009·The American Journal of Pathology·Torsten G LoofEva Medina
May 25, 2010·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Linda JohanssonAnna Norrby-Teglund
Aug 11, 2010·BMC Bioinformatics·Tina KoestlerIngo Ebersberger
Nov 26, 2010·Science·Pamela C Ronald, Bruce Beutler
Nov 30, 2010·Nucleic Acids Research·Adrian M AltenhoffChristophe Dessimoz
Dec 7, 2010·The Journal of Biological Chemistry·Zhongcheng ShiDekai Zhang
Dec 18, 2010·EMBO Reports·Sachin D DeshmukhPhilipp Henneke
Feb 18, 2011·The New England Journal of Medicine·Michael R Wessels
Aug 24, 2011·Journal of Innate Immunity·Annelies S ZinkernagelVictor Nizet
Sep 17, 2011·Nature Reviews. Microbiology·Jason N ColeMark J Walker
Oct 26, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Inbal MishalianEmanuel Hanski
Aug 17, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Asa HidmarkAlexander H Dalpke
Oct 31, 2012·ELife·Xiao-Dong Li, Zhijian James Chen
Nov 30, 2012·Nucleic Acids Research·UNKNOWN NCBI Resource Coordinators
Feb 19, 2013·Molecular Biology and Evolution·Bui Quang MinhArndt von Haeseler
Feb 22, 2013·ELife·Bettina L LeeGregory M Barton
Apr 27, 2013·Science·Amanda M JamiesonRuslan Medzhitov
Aug 29, 2014·PLoS Pathogens·James A TsatsaronisMartina L Sanderson-Smith
Sep 17, 2014·Infection and Immunity·Giacomo SignorinoConcetta Beninati
Oct 18, 2014·Frontiers in Cellular and Infection Microbiology·Christina Fieber, Pavel Kovarik
Oct 31, 2014·Proceedings of the National Academy of Sciences of the United States of America·Wenwen ShaYong-Jun Liu

❮ Previous
Next ❯

Citations

Mar 11, 2016·Cell Host & Microbe·Si Ming Man, Thirumala-Devi Kanneganti
Oct 27, 2015·Frontiers in Immunology·Christopher N LaRock, Victor Nizet
Mar 13, 2017·Cellular Immunology·Solmaz ShirjangKarim Shamsasenjan
Dec 12, 2017·Future Microbiology·J Andrés Valderrama, Victor Nizet
Oct 20, 2018·The Journal of Experimental Medicine·Yong Cheng, Jeffrey S Schorey
Oct 26, 2018·Proceedings of the National Academy of Sciences of the United States of America·Takashi ImaiSho Yamasaki
Nov 8, 2015·EMBO Reports·Anne KrügerCarsten J Kirschning
Jun 24, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tatjana EigenbrodAlexander H Dalpke
Jul 4, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tatjana Eigenbrod, Alexander H Dalpke
Feb 14, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Julia KolterPhilipp Henneke
Jan 14, 2017·Frontiers in Immunology·Pavel KovarikFlorian Ebner
Oct 21, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Allen WashingtonJack D Bui
Feb 16, 2019·Microbiology Spectrum·Vijay Pancholi

❮ Previous
Next ❯

Methods Mentioned

BETA
FCS
transfection
PMA
ELISA

Software Mentioned

OMA browser Blast
OMA browser Blast search
GraphPad Prism
FACT
OMA Browser
mafft
OMA Browse ( Feature Architecture Comparison Tool
iqtree TEST

Related Concepts

Related Feeds

Bacterial Pneumonia (ASM)

Bacterial pneumonia is a prevalent and costly infection that is a significant cause of morbidity and mortality in patients of all ages. Here is the latest research.

Bacterial Pneumonia

Bacterial pneumonia is a prevalent and costly infection that is a significant cause of morbidity and mortality in patients of all ages. Here is the latest research.

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.

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.