PMID- 25760420
OWN - NLM
STAT- MEDLINE
DCOM- 20160818
LR  - 20230203
IS  - 1935-3456 (Electronic)
IS  - 1933-0219 (Print)
IS  - 1933-0219 (Linking)
VI  - 8
IP  - 6
DP  - 2015 Nov
TI  - MyD88 dependence of beryllium-induced dendritic cell trafficking and CD4(+) T-cell 
      priming.
PG  - 1237-47
LID - 10.1038/mi.2015.14 [doi]
AB  - Beryllium exposure results in beryllium hypersensitivity in a subset of exposed 
      individuals, leading to granulomatous inflammation and fibrosis in the lung. In 
      addition to its antigenic properties, beryllium has potent adjuvant activity that 
      contributes to sensitization via unknown pathways. Here we show that beryllium 
      induces cellular death and release of interleukin (IL)-1alpha and DNA into the lung. 
      Release of IL-1alpha was inflammasome independent and required for beryllium-induced 
      neutrophil recruitment into the lung. Beryllium enhanced classical dendritic cell 
      (cDC) migration from the lung to draining lymph nodes (LNs) in an 
      IL-1R-independent manner, and the accumulation of activated cDCs in the LN was 
      associated with increased priming of CD4(+) T cells. DC migration was reduced in 
      Toll-like receptor 9 knockout (TLR9KO) mice; however, cDCs in the LNs of 
      TLR9-deficient mice were highly activated, suggesting a role for more than one 
      innate receptor in the effects on DCs. The adjuvant effects of beryllium on 
      CD4(+) T-cell priming were similar in wild-type, IL-1R-, caspase-1-, TLR2-, 
      TLR4-, TLR7-, and TLR9-deficient mice. In contrast, DC migration, activation, and 
      the adjuvant effects of beryllium were significantly reduced in myeloid 
      differentiation primary response gene 88 knockout (MyD88KO) mice. Collectively, 
      these data suggest that beryllium exposure results in the release of 
      damage-associated molecular patterns that engage MyD88-dependent receptors to 
      enhance pulmonary DC function.
FAU - McKee, A S
AU  - McKee AS
AD  - Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, 
      Colorado, USA.
FAU - Mack, D G
AU  - Mack DG
AD  - Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, 
      Colorado, USA.
FAU - Crawford, F
AU  - Crawford F
AD  - Department of Immunology, University of Colorado Anschutz Medical Campus, Aurora, 
      Colorado, USA.
AD  - Department of Biomedical Research, National Jewish Health, Denver, Colorado, USA.
FAU - Fontenot, A P
AU  - Fontenot AP
AD  - Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, 
      Colorado, USA.
AD  - Department of Immunology, University of Colorado Anschutz Medical Campus, Aurora, 
      Colorado, USA.
LA  - eng
GR  - R01 HL126736/HL/NHLBI NIH HHS/United States
GR  - R21 HL111760/HL/NHLBI NIH HHS/United States
GR  - HL111760/HL/NHLBI NIH HHS/United States
GR  - P01 ES011810/ES/NIEHS NIH HHS/United States
GR  - R01 HL062410/HL/NHLBI NIH HHS/United States
GR  - ES11810/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20150311
PL  - United States
TA  - Mucosal Immunol
JT  - Mucosal immunology
JID - 101299742
RN  - 0 (Myd88 protein, mouse)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - OW5102UV6N (Beryllium)
SB  - IM
MH  - Animals
MH  - Berylliosis/*immunology
MH  - Beryllium/toxicity
MH  - CD4-Positive T-Lymphocytes/*immunology
MH  - Cell Movement/*immunology
MH  - Dendritic Cells/*immunology
MH  - Disease Models, Animal
MH  - Flow Cytometry
MH  - Humans
MH  - Lymphocyte Activation/immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Myeloid Differentiation Factor 88/*immunology
MH  - Neutrophils/immunology
PMC - PMC4567547
MID - NIHMS660344
COIS- Disclosure: The authors have no conflicts of interest to declare.
EDAT- 2015/03/12 06:00
MHDA- 2016/08/19 06:00
PMCR- 2016/05/01
CRDT- 2015/03/12 06:00
PHST- 2014/10/02 00:00 [received]
PHST- 2015/01/12 00:00 [accepted]
PHST- 2015/03/12 06:00 [entrez]
PHST- 2015/03/12 06:00 [pubmed]
PHST- 2016/08/19 06:00 [medline]
PHST- 2016/05/01 00:00 [pmc-release]
AID - S1933-0219(22)01003-0 [pii]
AID - 10.1038/mi.2015.14 [doi]
PST - ppublish
SO  - Mucosal Immunol. 2015 Nov;8(6):1237-47. doi: 10.1038/mi.2015.14. Epub 2015 Mar 
      11.