PMID- 24695582
OWN - NLM
STAT- MEDLINE
DCOM- 20150129
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 4
DP  - 2014
TI  - TRAIL-R1 is a negative regulator of pro-inflammatory responses and modulates 
      long-term sequelae resulting from Chlamydia trachomatis infections in humans.
PG  - e93939
LID - 10.1371/journal.pone.0093939 [doi]
LID - e93939
AB  - The immune system eliminates Chlamydia trachomatis infection through 
      inflammation. However, uncontrolled inflammation can enhance pathology. In mice, 
      TNF-related apoptosis-inducing ligand receptor (TRAIL-R), known for its effects 
      on apoptosis, also regulates inflammation. In humans, the four homologues of 
      TRAIL-R had never been investigated for effects on inflammation. Here, we 
      examined whether TRAIL-R regulates inflammation during chlamydial infection. We 
      examined TRAIL-R1 single nucleotide polymorphisms (SNPs) in an Ecuadorian cohort 
      with and without C. trachomatis infections. There was a highly significant 
      association for the TRAIL+626 homozygous mutant GG for infection vs no infection 
      in this population. To confirm the results observed in the human population, 
      primary lung fibroblasts and bone marrow-derived macrophages (BMDMs) were 
      isolated from wildtype (WT) and TRAIL-R-deficient mice, and TRAIL-R1 levels in 
      human cervical epithelial cells were depleted by RNA interference. Infection of 
      BMDMs and primary lung fibroblasts with C. trachomatis strain L2, or the murine 
      pathogen C. muridarum, led to higher levels of MIP2 mRNA expression or IL-1beta 
      secretion from TRAIL-R-deficient cells than WT cells. Similarly, depletion of 
      TRAIL-R1 expression in human epithelial cells resulted in a higher level of IL-8 
      mRNA expression and protein secretion during C. trachomatis infection. We 
      conclude that human TRAIL-R1 SNPs and murine TRAIL-R modulate the innate immune 
      response against chlamydial infection. This is the first evidence that human 
      TRAIL-R1 is a negative regulator of inflammation and plays a role in modulating 
      Chlamydia pathogenesis.
FAU - Al-Kuhlani, Mufadhal
AU  - Al-Kuhlani M
AD  - Department of Molecular Cell Biology, and Health Sciences Research Institute, 
      University of California Merced, Merced, California, United States of America.
FAU - Rothschild, James
AU  - Rothschild J
FAU - Pal, Sukumar
AU  - Pal S
AD  - Department of Pathology and Laboratory Medicine, University of California Irvine, 
      Irvine, California, United States of America.
FAU - de la Maza, Luis M
AU  - de la Maza LM
AD  - Department of Pathology and Laboratory Medicine, University of California Irvine, 
      Irvine, California, United States of America.
FAU - Ouburg, Sander
AU  - Ouburg S
AD  - Laboratory of Immunogenetics, Medical Microbiology and Infection Prevention, 
      Research School V-ICI, VU University Medical Center, Amsterdam, The Netherlands.
FAU - Morre, Servaas A
AU  - Morre SA
AD  - Laboratory of Immunogenetics, Medical Microbiology and Infection Prevention, 
      Research School V-ICI, VU University Medical Center, Amsterdam, The Netherlands; 
      Institute of Public Health Genomics, Department of Genetics and Cell Biology, 
      Research School GROW, University of Maastricht, Maastricht, The Netherlands.
FAU - Dean, Deborah
AU  - Dean D
AD  - Center for Immunobiology and Vaccine Development, Children's Hospital Oakland 
      Research Institute, Oakland, California, United States of America; Graduate 
      Program in Bioengineering, University of California, Berkeley and San Francisco, 
      California, United States of America; Department of Medicine, University of 
      California San Francisco, San Francisco, California, United States of America.
FAU - Ojcius, David M
AU  - Ojcius DM
AD  - Department of Molecular Cell Biology, and Health Sciences Research Institute, 
      University of California Merced, Merced, California, United States of America.
LA  - eng
GR  - R01 AI032248/AI/NIAID NIH HHS/United States
GR  - R56 AI078419/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20140402
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Receptors, TNF-Related Apoptosis-Inducing Ligand)
SB  - IM
EIN - PLoS One. 2014;9(8):e106964. Rothchild, James [corrected to Rothschild, James]
MH  - Adolescent
MH  - Adult
MH  - Animals
MH  - Chlamydia Infections/*genetics/immunology/metabolism
MH  - Chlamydia trachomatis
MH  - Female
MH  - Fibroblasts/metabolism
MH  - *Genetic Predisposition to Disease
MH  - Genotype
MH  - Humans
MH  - Immunity, Innate/genetics
MH  - Inflammation/*genetics/immunology/metabolism
MH  - Lung/immunology/metabolism
MH  - Macrophages/metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Middle Aged
MH  - *Polymorphism, Single Nucleotide
MH  - Receptors, TNF-Related Apoptosis-Inducing Ligand/*genetics/metabolism
MH  - Young Adult
PMC - PMC3973638
COIS- Competing Interests: David Ojcius and Deborah Dean are editors for PLoS ONE. This 
      does not alter the authors' adherence to PLOS ONE Editorial policies and 
      criteria.
EDAT- 2014/04/04 06:00
MHDA- 2015/01/30 06:00
PMCR- 2014/04/02
CRDT- 2014/04/04 06:00
PHST- 2014/02/04 00:00 [received]
PHST- 2014/03/10 00:00 [accepted]
PHST- 2014/04/04 06:00 [entrez]
PHST- 2014/04/04 06:00 [pubmed]
PHST- 2015/01/30 06:00 [medline]
PHST- 2014/04/02 00:00 [pmc-release]
AID - PONE-D-14-05404 [pii]
AID - 10.1371/journal.pone.0093939 [doi]
PST - epublish
SO  - PLoS One. 2014 Apr 2;9(4):e93939. doi: 10.1371/journal.pone.0093939. eCollection 
      2014.