PMID- 24023674
OWN - NLM
STAT- MEDLINE
DCOM- 20140415
LR  - 20211201
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 8
DP  - 2013
TI  - TLR2 regulates neutrophil recruitment and cytokine production with minor 
      contributions from TLR9 during hypersensitivity pneumonitis.
PG  - e73143
LID - 10.1371/journal.pone.0073143 [doi]
LID - e73143
AB  - Hypersensitivity pneumonitis (HP) is an interstitial lung disease that develops 
      following repeated exposure to environmental antigens. The disease results in 
      alveolitis, granuloma formation and may progress to a fibrotic chronic form, 
      which is associated with significant morbidity and mortality. The severity of the 
      disease correlates with a neutrophil rich influx and an IL-17 response. We used 
      the Saccharopolysporarectivirgula (SR) model of HP to determine whether Toll-like 
      receptors (TLR) 2 and 9 cooperate in neutrophil recruitment and IL-17-associated 
      cytokine production during the development of HP. Stimulation of bone marrow 
      derived macrophages (BMDMs) from C57BL/6, MyD88(-/-) and TLR2/9(-/-) mice with SR 
      demonstrate that SR is a strong inducer of neutrophil chemokines and growth 
      factors. The cytokines induced by SR were MyD88-dependent and, of those, most 
      were partially or completely dependent on TLRs 2 and 9. Following in vivo 
      exposure to SR, CXCL2 production and neutrophil recruitment were reduced in 
      TLR2(-/-) and TLR2/9(-/-) mice suggesting that the response was largely dependent 
      on TLR2; however the reduction was greatest in the TLR2/9(-/-) double knockout 
      mice indicating TLR9 may also contribute to the response. There was a reduction 
      in the levels of pro-inflammatory cytokines TNFalpha and IL-6 as well as CCL3 and 
      CCL4 in the BALF from TLR2/9(-/-) mice compared to WT and single knockout (SKO) 
      mice exposed one time to SR. The decrease in neutrophil recruitment and TNFalpha 
      production in the TLR2/9(-/-) mice was maintained throughout 3 weeks of SR 
      exposures in comparison to WT and SKO mice. Both TLRs 2 and 9 contributed to the 
      Th17 response; there was a decrease in Th17 cells and IL-17 mRNA in the 
      TLR2/9(-/-) mice in comparison to the WT and SKO mice. Despite the effects on 
      neutrophil recruitment and the IL-17 response, TLR2/9(-/-) mice developed 
      granuloma formation similarly to WT and SKO mice suggesting that there are 
      additional mediators and pattern recognition receptors involved in the disease.
FAU - Andrews, Kelly
AU  - Andrews K
AD  - Department of Microbiology, Immunology and Biochemistry, University of Tennessee 
      Health Science Center, Memphis, Tennessee, United States of America.
FAU - Abdelsamed, Hossam
AU  - Abdelsamed H
FAU - Yi, Ae-Kyung
AU  - Yi AK
FAU - Miller, Mark A
AU  - Miller MA
FAU - Fitzpatrick, Elizabeth A
AU  - Fitzpatrick EA
LA  - eng
GR  - R01 AI053137/AI/NIAID NIH HHS/United States
GR  - R01 HL084172/HL/NHLBI NIH HHS/United States
GR  - HL084172/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20130830
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Chemokines)
RN  - 0 (Cytokines)
RN  - 0 (Tlr2 protein, mouse)
RN  - 0 (Tlr9 protein, mouse)
RN  - 0 (Toll-Like Receptor 2)
RN  - 0 (Toll-Like Receptor 9)
SB  - IM
MH  - Alveolitis, Extrinsic Allergic/complications/*immunology/microbiology/pathology
MH  - Animals
MH  - Chemokines/biosynthesis
MH  - Cytokines/*biosynthesis
MH  - Female
MH  - Granuloma/complications/pathology
MH  - Inflammation/complications/pathology
MH  - Lung/immunology/microbiology/pathology
MH  - Lymphocytes/immunology
MH  - Macrophages/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mutation/genetics
MH  - Neutrophil Infiltration/*immunology
MH  - Saccharopolyspora/physiology
MH  - Th1 Cells/immunology
MH  - Th17 Cells/immunology
MH  - Toll-Like Receptor 2/deficiency/*metabolism
MH  - Toll-Like Receptor 9/deficiency/*metabolism
PMC - PMC3758260
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/09/12 06:00
MHDA- 2014/04/16 06:00
PMCR- 2013/08/30
CRDT- 2013/09/12 06:00
PHST- 2013/02/28 00:00 [received]
PHST- 2013/07/25 00:00 [accepted]
PHST- 2013/09/12 06:00 [entrez]
PHST- 2013/09/12 06:00 [pubmed]
PHST- 2014/04/16 06:00 [medline]
PHST- 2013/08/30 00:00 [pmc-release]
AID - PONE-D-13-08876 [pii]
AID - 10.1371/journal.pone.0073143 [doi]
PST - epublish
SO  - PLoS One. 2013 Aug 30;8(8):e73143. doi: 10.1371/journal.pone.0073143. eCollection 
      2013.