PMID- 29162709
OWN - NLM
STAT- MEDLINE
DCOM- 20180731
LR  - 20191227
IS  - 2150-7511 (Electronic)
VI  - 8
IP  - 6
DP  - 2017 Nov 21
TI  - Ehrlichia chaffeensis and Its Invasin EtpE Block Reactive Oxygen Species 
      Generation by Macrophages in a DNase X-Dependent Manner.
LID - 10.1128/mBio.01551-17 [doi]
LID - e01551-17
AB  - The obligatory intracellular pathogen Ehrlichia chaffeensis lacks most genes that 
      confer resistance to oxidative stress but can block reactive oxygen species (ROS) 
      generation by host monocytes-macrophages. Bacterial and host molecules 
      responsible for this inhibition have not been identified. To infect host cells, 
      Ehrlichia uses the C terminus of its surface invasin, entry-triggering protein of 
      Ehrlichia (EtpE; EtpE-C), which directly binds the mammalian cell surface 
      receptor glycosylphosphatidylinositol-anchored protein DNase X. We investigated 
      whether EtpE-C binding to DNase X blocks ROS production by mouse bone 
      marrow-derived macrophages (BMDMs). On the basis of a luminol-dependent 
      chemiluminescence assay, E. chaffeensis inhibited phorbol myristate acetate 
      (PMA)-induced ROS generation by BMDMs from wild-type, but not DNase X(-/-), mice. 
      EtpE-C is critical for inhibition, as recombinant EtpE-C (rEtpE-C)-coated latex 
      beads, but not recombinant N-terminal EtpE-coated or uncoated beads, inhibited 
      PMA-induced ROS generation by BMDMs from wild-type mice. DNase X is required for 
      this inhibition, as none of these beads inhibited PMA-induced ROS generation by 
      BMDMs from DNase X(-/-) mice. Previous studies showed that E. chaffeensis does 
      not block ROS generation in neutrophils, a cell type that is a potent ROS 
      generator but is not infected by E. chaffeensis Human and mouse peripheral blood 
      neutrophils did not express DNase X. Our findings point to a unique survival 
      mechanism of ROS-sensitive obligate intramonocytic bacteria that involves invasin 
      EtpE binding to DNase X on the host cell surface. This is the first report of 
      bacterial invasin having such a subversive activity on ROS 
      generation.IMPORTANCEEhrlichia chaffeensis preferentially infects 
      monocytes-macrophages and causes a life-threatening emerging tick-transmitted 
      infectious disease called human monocytic ehrlichiosis. Ehrlichial infection, and 
      hence the disease, depends on the ability of this bacterium to avoid or overcome 
      powerful microbicidal mechanisms of host monocytes-macrophages, one of which is 
      the generation of ROS. Our findings reveal that an ehrlichial surface invasin, 
      EtpE, not only triggers bacterial entry but also blocks ROS generation by host 
      macrophages through its host cell receptor, DNase X. As ROS sensitivity is an 
      Achilles' heel of this group of pathogens, understanding the mechanism by which 
      E. chaffeensis rapidly blocks ROS generation suggests a new approach for 
      developing effective anti-infective measures. The discovery of a ROS-blocking 
      pathway is also important, as modulation of ROS generation is important in a 
      variety of ailments and biological processes.
CI  - Copyright (c) 2017 Teymournejad et al.
FAU - Teymournejad, Omid
AU  - Teymournejad O
AD  - Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, 
      USA.
FAU - Lin, Mingqun
AU  - Lin M
AD  - Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, 
      USA.
FAU - Rikihisa, Yasuko
AU  - Rikihisa Y
AD  - Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, 
      USA rikihisa.1@osu.edu.
LA  - eng
GR  - R01 AI121124/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20171121
PL  - United States
TA  - mBio
JT  - mBio
JID - 101519231
RN  - 0 (Adhesins, Bacterial)
RN  - 0 (Reactive Oxygen Species)
RN  - EC 3.1.- (Deoxyribonucleases)
SB  - IM
MH  - Adhesins, Bacterial/*immunology
MH  - Animals
MH  - Deoxyribonucleases/deficiency/genetics/*metabolism
MH  - Ehrlichia chaffeensis/genetics/*immunology/pathogenicity
MH  - Humans
MH  - Macrophages/*immunology/microbiology
MH  - Mice
MH  - Monocytes/immunology/microbiology
MH  - Neutrophils/immunology/microbiology
MH  - Reactive Oxygen Species/*immunology
MH  - Signal Transduction
PMC - PMC5698551
OTO - NOTNLM
OT  - DNase X
OT  - Ehrlichia
OT  - EtpE
OT  - macrophages
OT  - neutrophils
OT  - reactive oxygen species
EDAT- 2017/11/23 06:00
MHDA- 2018/08/01 06:00
PMCR- 2017/11/21
CRDT- 2017/11/23 06:00
PHST- 2017/11/23 06:00 [entrez]
PHST- 2017/11/23 06:00 [pubmed]
PHST- 2018/08/01 06:00 [medline]
PHST- 2017/11/21 00:00 [pmc-release]
AID - mBio.01551-17 [pii]
AID - mBio01551-17 [pii]
AID - 10.1128/mBio.01551-17 [doi]
PST - epublish
SO  - mBio. 2017 Nov 21;8(6):e01551-17. doi: 10.1128/mBio.01551-17.