PMID- 29394352
OWN - NLM
STAT- MEDLINE
DCOM- 20180925
LR  - 20181202
IS  - 2049-632X (Electronic)
IS  - 2049-632X (Linking)
VI  - 76
IP  - 2
DP  - 2018 Mar 1
TI  - Cyclic di-AMP-mediated interaction between Mycobacterium tuberculosis DeltacnpB and 
      macrophages implicates a novel strategy for improving BCG vaccination.
LID - 10.1093/femspd/fty008 [doi]
AB  - Cyclic di-AMP (c-di-AMP) has been shown to play an important role in bacterial 
      physiology and pathogen-host interactions. We previously reported that deletion 
      of the sole c-di-AMP phosphodiesterase-encoding gene (cnpB) in Mycobacterium 
      tuberculosis (Mtb) led to significant virulence attenuation. In this study, we 
      found that DeltacnpB of M. bovisbacillus Calmette-Guerin (BCG) was unable to secrete 
      c-di-AMP, which differs from Mtb DeltacnpB. We infected bone marrow-derived 
      macrophages (BMDMs) with c-di-AMP-associated mutants generated from both Mtb and 
      BCG. Our results showed that upon infection with Mtb DeltacnpB, BMDMs of wildtype 
      mice secreted a large amount of interferon-beta (IFN-beta) post-infection similarly as 
      we reported previously. In contrast, the response was less pronounced with BMDMs 
      isolated from cGAS-/- mice and was nearly abolished with BMDMs prepared from 
      STING-/- mice. Deletion of the region of difference 1 (RD1) locus in Mtb DeltacnpB 
      did not alter the c-di-AMP secretion of DeltacnpB but eliminated the IFN-beta production 
      in the infected cells. In contrast, neither BCG DeltacnpB nor a recombinant BCG DeltacnpB 
      with a pRD1 cosmid induced a type I interferon response. Interestingly, multiple 
      studies have demonstrated that type I IFN enhances BCG's immunity. Thus, amending 
      BCG based on our findings might improve BCG vaccination.
FAU - Zhang, Yang
AU  - Zhang Y
AD  - Department of Immunology and Microbial Disease, MC-151, Albany Medical College, 
      47 New Scotland Avenue, Albany, NY 12208-3479, USA.
FAU - Yang, Jun
AU  - Yang J
AD  - Department of Immunology and Microbial Disease, MC-151, Albany Medical College, 
      47 New Scotland Avenue, Albany, NY 12208-3479, USA.
FAU - Bai, Guangchun
AU  - Bai G
AD  - Department of Immunology and Microbial Disease, MC-151, Albany Medical College, 
      47 New Scotland Avenue, Albany, NY 12208-3479, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Pathog Dis
JT  - Pathogens and disease
JID - 101595366
RN  - 0 (BCG Vaccine)
RN  - 0 (Dinucleoside Phosphates)
RN  - 0 (cyclic diadenosine phosphate)
RN  - 77238-31-4 (Interferon-beta)
RN  - EC 3.1.4.17 (3',5'-Cyclic-AMP Phosphodiesterases)
SB  - IM
MH  - 3',5'-Cyclic-AMP Phosphodiesterases/deficiency/*metabolism
MH  - Animals
MH  - BCG Vaccine/*immunology
MH  - Cells, Cultured
MH  - Dinucleoside Phosphates/*metabolism
MH  - Interferon-beta/metabolism
MH  - Macrophages/*immunology/microbiology
MH  - Mice
MH  - Mice, Knockout
MH  - Mycobacterium bovis/enzymology/*immunology
MH  - Mycobacterium tuberculosis/enzymology/immunology
MH  - Tuberculosis/*prevention & control
MH  - Vaccination/*methods
EDAT- 2018/02/03 06:00
MHDA- 2018/09/27 06:00
CRDT- 2018/02/03 06:00
PHST- 2017/08/29 00:00 [received]
PHST- 2018/01/30 00:00 [accepted]
PHST- 2018/02/03 06:00 [pubmed]
PHST- 2018/09/27 06:00 [medline]
PHST- 2018/02/03 06:00 [entrez]
AID - 4831477 [pii]
AID - 10.1093/femspd/fty008 [doi]
PST - ppublish
SO  - Pathog Dis. 2018 Mar 1;76(2). doi: 10.1093/femspd/fty008.