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

Christina Fieber, Marton Janos, Tina Koestler, Nina Gratz, Xiao Dong Li, Virginia Castiglia, Marion Aberle, Martina Sauert, Mareike Wegner, Lena Alexopoulou, Carsten J. Kirschning, Zhijian J. Chen, Arndt Von Haeseler, Pavel Kovarik

Research output: Contribution to journalArticle

26 Citations (Scopus)

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 nonredundant 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.

Original languageEnglish (US)
Article numbere0119727
JournalPLoS One
Volume10
Issue number3
DOIs
StatePublished - Mar 10 2015

Fingerprint

Streptococcus pyogenes
Macrophages
Innate Immunity
Chemical activation
Mammals
Toll-Like Receptors
Pathogens
Rats
Animals
RNA
Cytokines
mice
macrophages
dendritic cells
Infection
innate immunity
phagocytosis
Phagocytosis
infection
Dendritic Cells

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Fieber, C., Janos, M., Koestler, T., Gratz, N., Li, X. D., Castiglia, V., ... Kovarik, P. (2015). Innate immune response to streptococcus pyogenes depends on the combined activation of TLR13 and TLR2. PLoS One, 10(3), [e0119727]. https://doi.org/10.1371/journal.pone.0119727

Innate immune response to streptococcus pyogenes depends on the combined activation of TLR13 and TLR2. / Fieber, Christina; Janos, Marton; Koestler, Tina; Gratz, Nina; Li, Xiao Dong; Castiglia, Virginia; Aberle, Marion; Sauert, Martina; Wegner, Mareike; Alexopoulou, Lena; Kirschning, Carsten J.; Chen, Zhijian J.; Von Haeseler, Arndt; Kovarik, Pavel.

In: PLoS One, Vol. 10, No. 3, e0119727, 10.03.2015.

Research output: Contribution to journalArticle

Fieber, C, Janos, M, Koestler, T, Gratz, N, Li, XD, Castiglia, V, Aberle, M, Sauert, M, Wegner, M, Alexopoulou, L, Kirschning, CJ, Chen, ZJ, Von Haeseler, A & Kovarik, P 2015, 'Innate immune response to streptococcus pyogenes depends on the combined activation of TLR13 and TLR2', PLoS One, vol. 10, no. 3, e0119727. https://doi.org/10.1371/journal.pone.0119727
Fieber, Christina ; Janos, Marton ; Koestler, Tina ; Gratz, Nina ; Li, Xiao Dong ; Castiglia, Virginia ; Aberle, Marion ; Sauert, Martina ; Wegner, Mareike ; Alexopoulou, Lena ; Kirschning, Carsten J. ; Chen, Zhijian J. ; Von Haeseler, Arndt ; Kovarik, Pavel. / Innate immune response to streptococcus pyogenes depends on the combined activation of TLR13 and TLR2. In: PLoS One. 2015 ; Vol. 10, No. 3.
@article{bde178cac05544f1b95370f23e9e8128,
title = "Innate immune response to streptococcus pyogenes depends on the combined activation of TLR13 and TLR2",
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 nonredundant 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.",
author = "Christina Fieber and Marton Janos and Tina Koestler and Nina Gratz and Li, {Xiao Dong} and Virginia Castiglia and Marion Aberle and Martina Sauert and Mareike Wegner and Lena Alexopoulou and Kirschning, {Carsten J.} and Chen, {Zhijian J.} and {Von Haeseler}, Arndt and Pavel Kovarik",
year = "2015",
month = "3",
day = "10",
doi = "10.1371/journal.pone.0119727",
language = "English (US)",
volume = "10",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "3",

}

TY - JOUR

T1 - Innate immune response to streptococcus pyogenes depends on the combined activation of TLR13 and TLR2

AU - Fieber, Christina

AU - Janos, Marton

AU - Koestler, Tina

AU - Gratz, Nina

AU - Li, Xiao Dong

AU - Castiglia, Virginia

AU - Aberle, Marion

AU - Sauert, Martina

AU - Wegner, Mareike

AU - Alexopoulou, Lena

AU - Kirschning, Carsten J.

AU - Chen, Zhijian J.

AU - Von Haeseler, Arndt

AU - Kovarik, Pavel

PY - 2015/3/10

Y1 - 2015/3/10

N2 - 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 nonredundant 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.

AB - 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 nonredundant 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.

UR - http://www.scopus.com/inward/record.url?scp=84924417249&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84924417249&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0119727

DO - 10.1371/journal.pone.0119727

M3 - Article

C2 - 25756897

AN - SCOPUS:84924417249

VL - 10

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 3

M1 - e0119727

ER -