PMID- 29624589
OWN - NLM
STAT- MEDLINE
DCOM- 20180716
LR  - 20181114
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 13
IP  - 4
DP  - 2018
TI  - Toll-like receptor 3 (TLR3) promotes the resolution of Chlamydia muridarum
      genital tract infection in congenic C57BL/6N mice.
PG  - e0195165
LID - 10.1371/journal.pone.0195165 [doi]
AB  - Chlamydia trachomatis urogenital serovars primarily replicate in epithelial cells
      lining the reproductive tract. Epithelial cells recognize Chlamydia through cell 
      surface and cytosolic receptors, and/or endosomal innate receptors such as
      Toll-like receptors (TLRs). Activation of these receptors triggers both innate
      and adaptive immune mechanisms that are required for chlamydial clearance, but
      are also responsible for the immunopathology in the reproductive tract. We
      previously demonstrated that Chlamydia muridarum (Cm) induces IFN-beta in oviduct
      epithelial cells (OE) in a TLR3-dependent manner, and that the synthesis of
      several cytokines and chemokines are diminished in Cm-challenged OE derived from 
      TLR3-/- 129S1 mice. Furthermore, our in vitro studies showed that Cm replication 
      in TLR3-/- OE is more efficient than in wild-type OE. Because TLR3 modulates the 
      release inflammatory mediators involved in host defense during Cm infection, we
      hypothesized that TLR3 plays a protective role against Cm-induced genital tract
      pathology in congenic C57BL/6N mice. Using the Cm mouse model for human Chlamydia
      genital tract infections, we demonstrated that TLR3-/- mice had increased Cm
      shedding during early and mid-stage genital infection. In early stage infection, 
      TLR3-/- mice showed a diminished synthesis of IFN-beta, IL-1beta, and IL-6, but
      enhanced production of IL-10, TNF-alpha, and IFN-gamma. In mid-stage infection,
      TLR3-/- mice exhibited significantly enhanced lymphocytic endometritis and
      salpingitis than wild-type mice. These lymphocytes were predominantly scattered
      along the endometrial stroma and the associated smooth muscle, and the lamina
      propria supporting the oviducts. Surprisingly, our data show that CD4+ T-cells
      are significantly enhanced in the genital tract TLR3-/- mice during mid-stage
      Chlamydial infection. In late-stage infections, both mouse strains developed
      hydrosalpinx; however, the extent of hydrosalpinx was more severe in TLR3-/-
      mice. Together, these data suggest that TLR3 promotes the clearance of Cm during 
      early and mid-stages of genital tract infection, and that loss of TLR3 is
      detrimental in the development hydrosalpinx.
FAU - Carrasco, Sebastian E
AU  - Carrasco SE
AD  - School of Veterinary Medicine and Comparative Pathology Laboratory, University of
      California-Davis, Davis, California, United States of America.
AD  - Department of Microbiology and Immunology, Indiana University School of Medicine,
      Indianapolis, Indiana, United States of America.
FAU - Hu, Sishun
AU  - Hu S
AD  - Department of Microbiology and Immunology, Indiana University School of Medicine,
      Indianapolis, Indiana, United States of America.
AD  - College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, People's
      Republic of China.
FAU - Imai, Denise M
AU  - Imai DM
AD  - School of Veterinary Medicine and Comparative Pathology Laboratory, University of
      California-Davis, Davis, California, United States of America.
FAU - Kumar, Ramesh
AU  - Kumar R
AD  - Department of Microbiology and Immunology, Indiana University School of Medicine,
      Indianapolis, Indiana, United States of America.
FAU - Sandusky, George E
AU  - Sandusky GE
AD  - Department of Pathology, Indiana University School of Medicine, Indianapolis,
      Indiana, United States of America.
FAU - Yang, X Frank
AU  - Yang XF
AD  - Department of Microbiology and Immunology, Indiana University School of Medicine,
      Indianapolis, Indiana, United States of America.
FAU - Derbigny, Wilbert A
AU  - Derbigny WA
AUID- ORCID: 0000-0002-8250-6261
AD  - Department of Microbiology and Immunology, Indiana University School of Medicine,
      Indianapolis, Indiana, United States of America.
LA  - eng
GR  - 1K22AI072072 /NH/NIH HHS/United States
GR  - 1R01AI104944 /NH/NIH HHS/United States
GR  - T32 AI 060519 /NH/NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20180406
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Cytokines)
RN  - 0 (Toll-Like Receptor 3)
SB  - IM
MH  - Animals
MH  - Chlamydia Infections/*genetics/metabolism/*microbiology/pathology
MH  - *Chlamydia muridarum
MH  - Cytokines/metabolism
MH  - *Disease Susceptibility
MH  - Female
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Reproductive Tract Infections/*genetics/metabolism/*microbiology/pathology
MH  - T-Lymphocyte Subsets/immunology/metabolism
MH  - Toll-Like Receptor 3/*genetics/metabolism
PMC - PMC5889059
EDAT- 2018/04/07 06:00
MHDA- 2018/07/17 06:00
CRDT- 2018/04/07 06:00
PHST- 2017/12/28 00:00 [received]
PHST- 2018/03/16 00:00 [accepted]
PHST- 2018/04/07 06:00 [entrez]
PHST- 2018/04/07 06:00 [pubmed]
PHST- 2018/07/17 06:00 [medline]
AID - 10.1371/journal.pone.0195165 [doi]
AID - PONE-D-17-45169 [pii]
PST - epublish
SO  - PLoS One. 2018 Apr 6;13(4):e0195165. doi: 10.1371/journal.pone.0195165.
      eCollection 2018.