PMID- 24901344
OWN - NLM
STAT- MEDLINE
DCOM- 20150813
LR  - 20240325
IS  - 1553-7374 (Electronic)
IS  - 1553-7366 (Print)
IS  - 1553-7366 (Linking)
VI  - 10
IP  - 6
DP  - 2014 Jun
TI  - Dusp3 and Psme3 are associated with murine susceptibility to Staphylococcus 
      aureus infection and human sepsis.
PG  - e1004149
LID - 10.1371/journal.ppat.1004149 [doi]
LID - e1004149
AB  - Using A/J mice, which are susceptible to Staphylococcus aureus, we sought to 
      identify genetic determinants of susceptibility to S. aureus, and evaluate their 
      function with regard to S. aureus infection. One QTL region on chromosome 11 
      containing 422 genes was found to be significantly associated with susceptibility 
      to S. aureus infection. Of these 422 genes, whole genome transcription profiling 
      identified five genes (Dcaf7, Dusp3, Fam134c, Psme3, and Slc4a1) that were 
      significantly differentially expressed in a) S. aureus -infected susceptible 
      (A/J) vs. resistant (C57BL/6J) mice and b) humans with S. aureus blood stream 
      infection vs. healthy subjects. Three of these genes (Dcaf7, Dusp3, and Psme3) 
      were down-regulated in susceptible vs. resistant mice at both pre- and 
      post-infection time points by qPCR. siRNA-mediated knockdown of Dusp3 and Psme3 
      induced significant increases of cytokine production in S. aureus-challenged 
      RAW264.7 macrophages and bone marrow derived macrophages (BMDMs) through 
      enhancing NF-kappaB signaling activity. Similar increases in cytokine production and 
      NF-kappaB activity were also seen in BMDMs from CSS11 (C57BL/6J background with 
      chromosome 11 from A/J), but not C57BL/6J. These findings suggest that Dusp3 and 
      Psme3 contribute to S. aureus infection susceptibility in A/J mice and play a 
      role in human S. aureus infection.
FAU - Yan, Qin
AU  - Yan Q
AD  - Division of Infectious Diseases & International Health, Department of Medicine, 
      Duke University School of Medicine, Durham, North Carolina, United States of 
      America.
FAU - Sharma-Kuinkel, Batu K
AU  - Sharma-Kuinkel BK
AD  - Division of Infectious Diseases & International Health, Department of Medicine, 
      Duke University School of Medicine, Durham, North Carolina, United States of 
      America.
FAU - Deshmukh, Hitesh
AU  - Deshmukh H
AD  - Division of Neonatology, Department of Pediatrics, Perelman School of Medicine, 
      University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
FAU - Tsalik, Ephraim L
AU  - Tsalik EL
AD  - Division of Infectious Diseases & International Health, Department of Medicine, 
      Duke University School of Medicine, Durham, North Carolina, United States of 
      America; Emergency Medicine Service, Durham Veteran's Affairs Medical Center, 
      Durham, North Carolina, United States of America; Duke Institute for Genome 
      Sciences & Policy, Duke University, Durham, North Carolina, United States of 
      America.
FAU - Cyr, Derek D
AU  - Cyr DD
AD  - Duke Institute for Genome Sciences & Policy, Duke University, Durham, North 
      Carolina, United States of America.
FAU - Lucas, Joseph
AU  - Lucas J
AD  - Quintiles Innovations, Morrisville, North Carolina, United States of America.
FAU - Woods, Christopher W
AU  - Woods CW
AD  - Division of Infectious Diseases & International Health, Department of Medicine, 
      Duke University School of Medicine, Durham, North Carolina, United States of 
      America; Duke Institute for Genome Sciences & Policy, Duke University, Durham, 
      North Carolina, United States of America; Section on Infectious Diseases, Durham 
      Veteran's Affairs Medical Center, Durham, North Carolina, United States of 
      America.
FAU - Scott, William K
AU  - Scott WK
AD  - Hussman Institute for Human Genomics, University of Miami Miller School of 
      Medicine, Miami, Florida, United States of America; Dr. John T. Macdonald 
      Foundation Department of Human Genetics, University of Miami Miller School of 
      Medicine, Miami, Florida, United States of America.
FAU - Sempowski, Gregory D
AU  - Sempowski GD
AD  - Duke Human Vaccine Institute, Durham, North Carolina, United States of America.
FAU - Thaden, Joshua T
AU  - Thaden JT
FAU - Rude, Thomas H
AU  - Rude TH
AD  - Division of Infectious Diseases & International Health, Department of Medicine, 
      Duke University School of Medicine, Durham, North Carolina, United States of 
      America.
FAU - Ahn, Sun Hee
AU  - Ahn SH
AD  - Department of Biochemistry School of Dentistry, Chonnam National University, 
      Bukgu, Gwangju, Korea.
FAU - Fowler, Vance G Jr
AU  - Fowler VG Jr
AD  - Division of Infectious Diseases & International Health, Department of Medicine, 
      Duke University School of Medicine, Durham, North Carolina, United States of 
      America; Duke Institute for Genome Sciences & Policy, Duke University, Durham, 
      North Carolina, United States of America; Duke Clinical Research Institute, 
      Durham, North Carolina, United States of America.
LA  - eng
GR  - IK2 CX000530/CX/CSRD VA/United States
GR  - K24 AI093969/AI/NIAID NIH HHS/United States
GR  - R01 AI068804/AI/NIAID NIH HHS/United States
GR  - UC6 AI058607/AI/NIAID NIH HHS/United States
PT  - Journal Article
DEP - 20140605
PL  - United States
TA  - PLoS Pathog
JT  - PLoS pathogens
JID - 101238921
RN  - 0 (Autoantigens)
RN  - 0 (Ki antigen)
RN  - 0 (Recombinant Proteins)
RN  - EC 3.1.3.48 (DUSP3 protein, human)
RN  - EC 3.1.3.48 (Dual Specificity Phosphatase 3)
RN  - EC 3.1.3.48 (Dusp3 protein, mouse)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
SB  - IM
EIN - PLoS Pathog. 2014 Jun;10(6):e1004259. Thaden, Joshua [corrected to Thaden, Joshua 
      T]
MH  - Animals
MH  - Animals, Genetically Modified
MH  - Autoantigens/chemistry/*genetics/metabolism
MH  - Bacteremia/*genetics/immunology/metabolism/microbiology
MH  - Cell Line, Transformed
MH  - Cells, Cultured
MH  - *Disease Susceptibility
MH  - Dual Specificity Phosphatase 3/antagonists & inhibitors/*genetics/metabolism
MH  - Female
MH  - *Gene Expression Regulation
MH  - Genome-Wide Association Study
MH  - Humans
MH  - Immunity, Innate
MH  - Macrophages/cytology/immunology/metabolism/microbiology
MH  - Male
MH  - Mice
MH  - Proteasome Endopeptidase Complex/chemistry/*genetics/metabolism
MH  - RNA Interference
MH  - Recombinant Proteins/chemistry/metabolism
MH  - Staphylococcal Infections/*genetics/immunology/metabolism/microbiology
PMC - PMC4047107
COIS- VGF served as Chair of V710 Scientific Advisory Committee (Merck), has received 
      grant support from Cerexa, Pfizer, Advanced Liquid Logic, MedImmune, has been a 
      paid consultant for Merck, Astellas, Affinium, Bayer, Theravance, Cubist, Cerexa, 
      Durata, Pfizer, NovaDigm, Novartis, Medicines Company, Biosynexus, MedImmune, and 
      Inimex, and has received honoraria from Merck, Astellas, Cubist, Pfizer, 
      Theravance, and Novartis. JL is employed by Quintiles Innovations. This does not 
      alter our adherence to all PLOS policies on sharing data and materials.
EDAT- 2014/06/06 06:00
MHDA- 2015/08/14 06:00
PMCR- 2014/06/05
CRDT- 2014/06/06 06:00
PHST- 2013/12/10 00:00 [received]
PHST- 2014/04/12 00:00 [accepted]
PHST- 2014/06/06 06:00 [entrez]
PHST- 2014/06/06 06:00 [pubmed]
PHST- 2015/08/14 06:00 [medline]
PHST- 2014/06/05 00:00 [pmc-release]
AID - PPATHOGENS-D-13-03248 [pii]
AID - 10.1371/journal.ppat.1004149 [doi]
PST - epublish
SO  - PLoS Pathog. 2014 Jun 5;10(6):e1004149. doi: 10.1371/journal.ppat.1004149. 
      eCollection 2014 Jun.