PMID- 30846984
OWN - NLM
STAT- MEDLINE
DCOM- 20200116
LR  - 20200309
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 10
DP  - 2019
TI  - Crucial Role of Nucleic Acid Sensing via Endosomal Toll-Like Receptors for the 
      Defense of Streptococcus pyogenes in vitro and in vivo.
PG  - 198
LID - 10.3389/fimmu.2019.00198 [doi]
LID - 198
AB  - Streptococcus pyogenes is a major human pathogen causing a variety of diseases 
      ranging from common pharyngitis to life-threatening soft tissue infections and 
      sepsis. Microbial nucleic acids, especially bacterial RNA, have recently been 
      recognized as a major group of pathogen-associated molecular patterns (PAMPs) 
      involved in the detection of Streptococcus pyogenes via endosomal Toll-like 
      receptors (TLRs) in vitro. However, the individual contribution and cooperation 
      between TLRs as well as cell-type and strain specific differences in dependency 
      on nucleic acid detection during S. pyogenes infection in vitro have not been 
      clarified in detail. Moreover, the role of particularly bacterial RNA for the 
      defense of S. pyogenes infection in vivo remains poorly defined. In this study, 
      we report that in all investigated innate immune cells involved in the resolution 
      of bacterial infections, including murine macrophages, dendritic cells and 
      neutrophils, recognition of S. pyogenes strain ATCC12344 is almost completely 
      dependent on nucleic acid sensing via endosomal TLRs at lower MOIs, whereas at 
      higher MOIs, detection via TLR2 plays an additional, yet redundant role. We 
      further demonstrate that different S. pyogenes strains display a considerable 
      inter-strain variability with respect to their nucleic acid dependent 
      recognition. Moreover, TLR13-dependent recognition of S. pyogenes RNA is largely 
      non-redundant in bone marrow-derived macrophages (BMDMs), but less relevant in 
      neutrophils and bone marrow-derived myeloid dendritic cells (BMDCs) for the 
      induction of an innate immune response in vitro. In vivo, we show that a loss of 
      nucleic acid sensing blunts early recognition of S. pyogenes, leading to a 
      reduced local containment of the bacterial infection with subsequent pronounced 
      systemic inflammation at later time points. Thus, our results argue for a crucial 
      role of nucleic acid sensing via endosomal TLRs in defense of S. pyogenes 
      infection both in vitro and in vivo.
FAU - Hafner, Anna
AU  - Hafner A
AD  - Department of Infectious Diseases, Medical Microbiology and Hygiene, Heidelberg 
      University Hospital, Heidelberg, Germany.
AD  - Department of Anesthesiology, Heidelberg University Hospital, Heidelberg, 
      Germany.
FAU - Kolbe, Ulrike
AU  - Kolbe U
AD  - Department of Infectious Diseases, Medical Microbiology and Hygiene, Heidelberg 
      University Hospital, Heidelberg, Germany.
FAU - Freund, Isabel
AU  - Freund I
AD  - Department of Infectious Diseases, Medical Microbiology and Hygiene, Heidelberg 
      University Hospital, Heidelberg, Germany.
FAU - Castiglia, Virginia
AU  - Castiglia V
AD  - Max F. Perutz Laboratories, University of Vienna, Vienna Biocenter, Vienna, 
      Austria.
FAU - Kovarik, Pavel
AU  - Kovarik P
AD  - Max F. Perutz Laboratories, University of Vienna, Vienna Biocenter, Vienna, 
      Austria.
FAU - Poth, Tanja
AU  - Poth T
AD  - Center for Model System and Comparative Pathology, Institute of Pathology, 
      Heidelberg University Hospital, Heidelberg, Germany.
FAU - Herster, Franziska
AU  - Herster F
AD  - Department of Immunology, Interfaculty Institute of Cell Biology, 
      Eberhard-Karls-University, Tubingen, Germany.
FAU - Weigand, Markus A
AU  - Weigand MA
AD  - Department of Anesthesiology, Heidelberg University Hospital, Heidelberg, 
      Germany.
FAU - Weber, Alexander N R
AU  - Weber ANR
AD  - Department of Immunology, Interfaculty Institute of Cell Biology, 
      Eberhard-Karls-University, Tubingen, Germany.
FAU - Dalpke, Alexander H
AU  - Dalpke AH
AD  - Department of Infectious Diseases, Medical Microbiology and Hygiene, Heidelberg 
      University Hospital, Heidelberg, Germany.
AD  - Institute of Medical Microbiology and Hygiene, Technical University Dresden, 
      Dresden, Germany.
FAU - Eigenbrod, Tatjana
AU  - Eigenbrod T
AD  - Department of Infectious Diseases, Medical Microbiology and Hygiene, Heidelberg 
      University Hospital, Heidelberg, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190221
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Biomarkers)
RN  - 0 (Cytokines)
RN  - 0 (Nucleic Acids)
RN  - 0 (RNA, Bacterial)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Toll-Like Receptors)
RN  - 31C4KY9ESH (Nitric Oxide)
SB  - IM
MH  - Biomarkers
MH  - Cytokines/metabolism
MH  - Endosomes/*metabolism
MH  - Host-Pathogen Interactions/*immunology
MH  - Humans
MH  - Immunity, Cellular
MH  - Immunity, Innate
MH  - Nitric Oxide/metabolism
MH  - Nucleic Acids/immunology
MH  - RNA, Bacterial/immunology
MH  - Reactive Oxygen Species/metabolism
MH  - Streptococcal Infections/*immunology/*metabolism/microbiology
MH  - Streptococcus pyogenes/*physiology
MH  - Toll-Like Receptors/*metabolism
PMC - PMC6394247
OTO - NOTNLM
OT  - Streptococcus pyogenes
OT  - TLR13
OT  - UNC93B1
OT  - bacterial RNA
OT  - innate immunity
OT  - nucleic acids
OT  - skin infection
EDAT- 2019/03/09 06:00
MHDA- 2020/01/17 06:00
PMCR- 2019/01/01
CRDT- 2019/03/09 06:00
PHST- 2018/08/20 00:00 [received]
PHST- 2019/01/23 00:00 [accepted]
PHST- 2019/03/09 06:00 [entrez]
PHST- 2019/03/09 06:00 [pubmed]
PHST- 2020/01/17 06:00 [medline]
PHST- 2019/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2019.00198 [doi]
PST - epublish
SO  - Front Immunol. 2019 Feb 21;10:198. doi: 10.3389/fimmu.2019.00198. eCollection 
      2019.