PMID- 36688662
OWN - NLM
STAT- MEDLINE
DCOM- 20230222
LR  - 20230821
IS  - 1098-5522 (Electronic)
IS  - 0019-9567 (Print)
IS  - 0019-9567 (Linking)
VI  - 91
IP  - 2
DP  - 2023 Feb 16
TI  - TGF-beta/IFN-gamma Antagonism in Subversion and Self-Defense of Phase II Coxiella 
      burnetii-Infected Dendritic Cells.
PG  - e0032322
LID - 10.1128/iai.00323-22 [doi]
LID - e00323-22
AB  - Dendritic cells (DCs) belong to the first line of innate defense and come into 
      early contact with invading pathogens, including the zoonotic bacterium Coxiella 
      burnetii, the causative agent of Q fever. However, the pathogen-host cell 
      interactions in C. burnetii-infected DCs, particularly the role of mechanisms of 
      immune subversion beyond virulent phase I lipopolysaccharide (LPS), as well as 
      the contribution of cellular self-defense strategies, are not understood. Using 
      phase II Coxiella-infected DCs, we show that impairment of DC maturation and MHC 
      I downregulation is caused by autocrine release and action of immunosuppressive 
      transforming growth factor-beta (TGF-beta). Our study demonstrates that IFN-gamma reverses 
      TGF-beta impairment of maturation/MHC I presentation in infected DCs and activates 
      bacterial elimination, predominantly by inducing iNOS/NO. Induced NO synthesis 
      strongly affects bacterial growth and infectivity. Moreover, our studies hint 
      that Coxiella-infected DCs might be able to protect themselves from mitotoxic NO 
      by switching from oxidative phosphorylation to glycolysis, thus ensuring survival 
      in self-defense against C. burnetii. Our results provide new insights into DC 
      subversion by Coxiella and the IFN-gamma-mediated targeting of C. burnetii during 
      early steps in the innate immune response.
FAU - Matthiesen, Svea
AU  - Matthiesen S
AD  - Institute of Immunology, Friedrich-Loeffler-Institut, Federal Research Institute 
      of Animal Health, Isle of Riems, Germany.
FAU - Christiansen, Bahne
AU  - Christiansen B
AD  - Institute of Immunology, Friedrich-Loeffler-Institut, Federal Research Institute 
      of Animal Health, Isle of Riems, Germany.
AD  - Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, 
      Federal Research Institute of Animal Health, Isle of Riems, Germany.
FAU - Jahnke, Rico
AU  - Jahnke R
AD  - Institute of Immunology, Friedrich-Loeffler-Institut, Federal Research Institute 
      of Animal Health, Isle of Riems, Germany.
FAU - Zaeck, Luca M
AU  - Zaeck LM
AD  - Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, 
      Federal Research Institute of Animal Health, Isle of Riems, Germany.
FAU - Karger, Axel
AU  - Karger A
AUID- ORCID: 0000-0002-0054-7394
AD  - Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, 
      Federal Research Institute of Animal Health, Isle of Riems, Germany.
FAU - Finke, Stefan
AU  - Finke S
AD  - Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, 
      Federal Research Institute of Animal Health, Isle of Riems, Germany.
FAU - Franzke, Kati
AU  - Franzke K
AD  - Institute of Infectology, Friedrich-Loeffler-Institut, Federal Research Institute 
      of Animal Health, Isle of Riems, Germany.
FAU - Knittler, Michael R
AU  - Knittler MR
AUID- ORCID: 0000-0002-1603-9861
AD  - Institute of Immunology, Friedrich-Loeffler-Institut, Federal Research Institute 
      of Animal Health, Isle of Riems, Germany.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230123
PL  - United States
TA  - Infect Immun
JT  - Infection and immunity
JID - 0246127
RN  - 0 (Transforming Growth Factor beta)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Humans
MH  - *Coxiella burnetii
MH  - Transforming Growth Factor beta
MH  - *Q Fever/microbiology
MH  - Interferon-gamma
MH  - Dendritic Cells
PMC - PMC9933720
OTO - NOTNLM
OT  - Coxiella burnetii
OT  - immune subversion
OT  - major histocompatibility complex
COIS- The authors declare no conflict of interest.
EDAT- 2023/01/24 06:00
MHDA- 2023/02/22 06:00
PMCR- 2023/07/23
CRDT- 2023/01/23 09:04
PHST- 2023/01/24 06:00 [pubmed]
PHST- 2023/02/22 06:00 [medline]
PHST- 2023/01/23 09:04 [entrez]
PHST- 2023/07/23 00:00 [pmc-release]
AID - 00323-22 [pii]
AID - iai.00323-22 [pii]
AID - 10.1128/iai.00323-22 [doi]
PST - ppublish
SO  - Infect Immun. 2023 Feb 16;91(2):e0032322. doi: 10.1128/iai.00323-22. Epub 2023 
      Jan 23.