PMID- 22315281
OWN - NLM
STAT- MEDLINE
DCOM- 20120416
LR  - 20120604
IS  - 1537-6613 (Electronic)
IS  - 0022-1899 (Linking)
VI  - 205
IP  - 6
DP  - 2012 Mar 15
TI  - Species-specific recognition of Aspergillus fumigatus by Toll-like receptor 1 and 
      Toll-like receptor 6.
PG  - 944-54
LID - 10.1093/infdis/jir882 [doi]
AB  - BACKGROUND: Aspergillus fumigatus causes invasive aspergillosis, a potentially 
      fatal infection in oncohematological patients. Innate immune detection of A. 
      fumigatus involves Toll-like receptor (TLR) 4 and TLR2, which forms a heterodimer 
      with either TLR1 or TLR6. The role of those coreceptors in Aspergillus sensing is 
      unknown. METHODS: Cytokine production was measured in bone marrow-derived 
      macrophages (BMDMs) from wild-type (WT) and TLR-deficient mice after incubation 
      with a WT and an immunogenic RodA-deficient (DeltarodA-47) strain of A. fumigatus and 
      in lungs from these mice after intranasal mold inoculation. Aspergillus 
      fumigatus-mediated NF-kappaB activation was measured in HEK293T cells transfected 
      with plasmids expressing mouse or human TLRs. RESULTS: Bone marrow-derived 
      macrophages from TLR1- and TLR6-deficient mice produced lower amounts of 
      interleukin 12p40, CXCL2, interleukin 6, and tumor necrosis factor alpha than BMDMs 
      from WT mice after stimulation with A. fumigatus. Lungs from TLR1- and 
      TLR6-deficient mice had diminished CXCL1 and CXCL2 production and increased 
      fungal burden after intranasal inoculation of DeltarodA A. fumigatus compared with 
      lungs from WT mice. DeltarodA strain-mediated NF-kappaB activation was observed in 
      HEK293T cells expressing mouse TLR2/1, mouse TLR2/6, and human TLR2/1 but not 
      human TLR2/6. CONCLUSIONS: Innate immune detection of A. fumigatus is mediated by 
      TLR4 and TLR2 together with TLR1 or TLR6 in mice and TLR1 but not TLR6 in humans.
FAU - Rubino, Ivana
AU  - Rubino I
AD  - Department of Medicine, University of Lausanne, Switzerland.
FAU - Coste, Alix
AU  - Coste A
FAU - Le Roy, Didier
AU  - Le Roy D
FAU - Roger, Thierry
AU  - Roger T
FAU - Jaton, Katia
AU  - Jaton K
FAU - Boeckh, Michael
AU  - Boeckh M
FAU - Monod, Michel
AU  - Monod M
FAU - Latge, Jean-Paul
AU  - Latge JP
FAU - Calandra, Thierry
AU  - Calandra T
FAU - Bochud, Pierre-Yves
AU  - Bochud PY
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120207
PL  - United States
TA  - J Infect Dis
JT  - The Journal of infectious diseases
JID - 0413675
RN  - 0 (Chemokine CXCL2)
RN  - 0 (Cxcl2 protein, mouse)
RN  - 0 (Interleukin-12 Subunit p40)
RN  - 0 (Interleukin-6)
RN  - 0 (NF-kappa B)
RN  - 0 (Tlr6 protein, mouse)
RN  - 0 (Toll-Like Receptor 1)
RN  - 0 (Toll-Like Receptor 6)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Animals
MH  - Aspergillosis/genetics
MH  - Aspergillus fumigatus/*pathogenicity
MH  - Chemokine CXCL2/metabolism
MH  - Female
MH  - *Gene Deletion
MH  - HEK293 Cells
MH  - Humans
MH  - Immunity, Innate
MH  - Interleukin-12 Subunit p40/biosynthesis
MH  - Interleukin-6/biosynthesis
MH  - Macrophages/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - NF-kappa B/metabolism
MH  - Species Specificity
MH  - Toll-Like Receptor 1/*metabolism
MH  - Toll-Like Receptor 6/*metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
EDAT- 2012/02/09 06:00
MHDA- 2012/04/17 06:00
CRDT- 2012/02/09 06:00
PHST- 2012/02/09 06:00 [entrez]
PHST- 2012/02/09 06:00 [pubmed]
PHST- 2012/04/17 06:00 [medline]
AID - jir882 [pii]
AID - 10.1093/infdis/jir882 [doi]
PST - ppublish
SO  - J Infect Dis. 2012 Mar 15;205(6):944-54. doi: 10.1093/infdis/jir882. Epub 2012 
      Feb 7.