PMID- 34017340
OWN - NLM
STAT- MEDLINE
DCOM- 20211014
LR  - 20211014
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 12
DP  - 2021
TI  - Mycobacterium tuberculosis Rv2145c Promotes Intracellular Survival by STAT3 and 
      IL-10 Receptor Signaling.
PG  - 666293
LID - 10.3389/fimmu.2021.666293 [doi]
LID - 666293
AB  - Although Mycobacterium tuberculosis (Mtb) is an intracellular pathogen in 
      phagocytic cells, the factors and mechanisms by which they invade and persist in 
      host cells are still not well understood. Characterization of the bacterial 
      proteins modulating macrophage function is essential for understanding 
      tuberculosis pathogenesis and bacterial virulence. Here we investigated the 
      pathogenic role of the Rv2145c protein in stimulating IL-10 production. We first 
      found that recombinant Rv2145c stimulated bone marrow-derived macrophages (BMDMs) 
      to secrete IL-10, IL-6 and TNF-alpha but not IL-12p70 and to increase the expression 
      of surface molecules through the MAPK, NF-kappaB, and TLR4 pathways and enhanced 
      STAT3 activation and the expression of IL-10 receptor in Mtb-infected BMDMs. 
      Rv2145c significantly enhanced intracellular Mtb growth in BMDMs compared with 
      that in untreated cells, which was abrogated by STAT3 inhibition and IL-10 
      receptor (IL-10R) blockade. Expression of Rv2145c in Mycobacterium smegmatis (M. 
      smegmatis) led to STAT3-dependent IL-10 production and enhancement of 
      intracellular growth in BMDMs. Furthermore, the clearance of Rv2145c-expressing 
      M. smegmatis in the lungs and spleens of mice was delayed, and these effects were 
      abrogated by administration of anti-IL-10R antibodies. Finally, all mice infected 
      with Rv2145c-expressing M. smegmatis died, but those infected with the vector 
      control strain did not. Our data suggest that Rv2145c plays a role in creating a 
      favorable environment for bacterial survival by modulating host signals.
CI  - Copyright (c) 2021 Park, Back, Jang, Lee, Son, Choi, Dang and Kim.
FAU - Park, Hye-Soo
AU  - Park HS
AD  - Department of Microbiology and Medical Science, and Translational Immunology 
      Institute, College of Medicine, Chungnam National University, Daejeon, South 
      Korea.
FAU - Back, Yong Woo
AU  - Back YW
AD  - Department of Microbiology and Medical Science, and Translational Immunology 
      Institute, College of Medicine, Chungnam National University, Daejeon, South 
      Korea.
FAU - Jang, In-Taek
AU  - Jang IT
AD  - Department of Microbiology and Medical Science, and Translational Immunology 
      Institute, College of Medicine, Chungnam National University, Daejeon, South 
      Korea.
FAU - Lee, Kang-In
AU  - Lee KI
AD  - Department of Microbiology and Medical Science, and Translational Immunology 
      Institute, College of Medicine, Chungnam National University, Daejeon, South 
      Korea.
FAU - Son, Yeo-Jin
AU  - Son YJ
AD  - Department of Microbiology and Medical Science, and Translational Immunology 
      Institute, College of Medicine, Chungnam National University, Daejeon, South 
      Korea.
FAU - Choi, Han-Gyu
AU  - Choi HG
AD  - Department of Microbiology and Medical Science, and Translational Immunology 
      Institute, College of Medicine, Chungnam National University, Daejeon, South 
      Korea.
FAU - Dang, Thi Binh
AU  - Dang TB
AD  - Department of Microbiology and Medical Science, and Translational Immunology 
      Institute, College of Medicine, Chungnam National University, Daejeon, South 
      Korea.
FAU - Kim, Hwa-Jung
AU  - Kim HJ
AD  - Department of Microbiology and Medical Science, and Translational Immunology 
      Institute, College of Medicine, Chungnam National University, Daejeon, South 
      Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210504
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Bacterial Proteins)
RN  - 0 (IL10 protein, mouse)
RN  - 0 (Receptors, Interleukin-10)
RN  - 0 (Recombinant Proteins)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (Stat3 protein, mouse)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
RN  - 130068-27-8 (Interleukin-10)
SB  - IM
MH  - Animals
MH  - Bacterial Proteins/genetics/*immunology
MH  - Interleukin-10/metabolism
MH  - Macrophage Activation
MH  - Macrophages/immunology/microbiology
MH  - Mice
MH  - Microbial Viability/genetics
MH  - Mycobacterium smegmatis/genetics/growth & development/immunology/pathogenicity
MH  - Mycobacterium tuberculosis/genetics/growth & 
      development/immunology/*pathogenicity
MH  - Receptors, Interleukin-10/antagonists & inhibitors/*metabolism
MH  - Recombinant Proteins/genetics/immunology
MH  - STAT3 Transcription Factor/antagonists & inhibitors/*metabolism
MH  - Signal Transduction
MH  - Toll-Like Receptor 4/metabolism
MH  - Virulence
PMC - PMC8129509
OTO - NOTNLM
OT  - IL-10
OT  - Mycobacterium tuberculosis
OT  - Rv2145c
OT  - STAT3
OT  - pathogenic role
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/05/22 06:00
MHDA- 2021/10/15 06:00
PMCR- 2021/01/01
CRDT- 2021/05/21 06:31
PHST- 2021/02/10 00:00 [received]
PHST- 2021/04/20 00:00 [accepted]
PHST- 2021/05/21 06:31 [entrez]
PHST- 2021/05/22 06:00 [pubmed]
PHST- 2021/10/15 06:00 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2021.666293 [doi]
PST - epublish
SO  - Front Immunol. 2021 May 4;12:666293. doi: 10.3389/fimmu.2021.666293. eCollection 
      2021.