PMID- 27148227
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20160505
LR  - 20201001
IS  - 1664-302X (Print)
IS  - 1664-302X (Electronic)
IS  - 1664-302X (Linking)
VI  - 7
DP  - 2016
TI  - Insufficient Generation of Mycobactericidal Mediators and Inadequate Level of 
      Phagosomal Maturation Are Related with Susceptibility to Virulent Mycobacterium 
      tuberculosis Infection in Mouse Macrophages.
PG  - 541
LID - 10.3389/fmicb.2016.00541 [doi]
LID - 541
AB  - Tuberculosis is caused by Mycobacterium tuberculosis infection, and it remains 
      major life-threatening infectious diseases worldwide. Although, M. tuberculosis 
      has infected one-third of the present human population, only 5-10% of 
      immunocompetent individuals are genetically susceptible to tuberculosis. All 
      inbred strains of mice are susceptible to tuberculosis; however, some mouse 
      strains are much more susceptible than others. In a previous report, we showed 
      that Th1-mediated immunity was not responsible for the differential 
      susceptibility between mouse models. To examine whether these susceptibility 
      differences between inbred mouse strains are due to the insufficient production 
      of effector molecules in the early stage of innate immunity, we investigated 
      mycobacteriostatic function of bone marrow-derived macrophages (BMDMs) in 
      resistant (BALB/c and C57BL/6) and susceptible strains (DBA/2) that were infected 
      with virulent M. tuberculosis (H37Rv) or attenuated M. tuberculosis (H37Ra). The 
      growth rate of virulent M. tuberculosis in infected cells was significantly 
      higher in DBA/2 BMDMs, whereas the growth of the attenuated strain was similar in 
      the three inbred mouse BMDM strains. In addition, the death rate of M. 
      tuberculosis-infected cells increased with the infectious dose when DBA/2 BMDMs 
      were infected with H37Rv. The intracellular reactive oxygen species level was 
      lower in DBA/2 BMDMs that were infected with virulent M. tuberculosis at an early 
      post-infection time point. The expression levels of phagosomal maturation 
      markers, including early endosomal antigen-1 (EEA1) and lysosome-associated 
      membrane protein-1 (LAMP-1), were significantly decreased in DBA/2 BMDM that were 
      infected with virulent M. tuberculosis, whereas IFNgamma-treatment restored the 
      phagosomal maturation activity. The nitric oxide (NO) production levels were also 
      significantly lower in DBA/2 BMDMs that were infected with virulent H37Rv at late 
      post-infection points; however, this was not observed with the attenuated H37Ra 
      strain. Furthermore, IFNgamma-treatment rescued the low NO production level and 
      insufficient M. tuberculosis growth control of DBA/2 BMDMs to the same level as 
      of both resistant strains. The secreted TNF-alpha and IL-10 level were not 
      significantly different between strains. Therefore, our findings suggest that 
      DBA/2 BMDMs may have defects in the phagosomal maturation process and in 
      inflammatory mediator production, as they showed innate immune defects when 
      infected with the virulent, but not attenuated M. tuberculosis strain.
FAU - Lee, Hyo-Ji
AU  - Lee HJ
AD  - Department of Biological Sciences and BIT Medical Convergence Graduate Program, 
      Kangwon National University Chuncheon, South Korea.
FAU - Ko, Hyun-Jeong
AU  - Ko HJ
AD  - College of Pharmacy, Kangwon National University Chuncheon, South Korea.
FAU - Jung, Yu-Jin
AU  - Jung YJ
AD  - Department of Biological Sciences and BIT Medical Convergence Graduate Program, 
      Kangwon National University Chuncheon, South Korea.
LA  - eng
PT  - Journal Article
DEP - 20160418
PL  - Switzerland
TA  - Front Microbiol
JT  - Frontiers in microbiology
JID - 101548977
PMC - PMC4834433
OTO - NOTNLM
OT  - Mycobacterium tuberculosis
OT  - macrophage
OT  - nitric oxide (NO)
OT  - phagosomal maturation
OT  - reactive oxygen species (ROS)
OT  - susceptibility
EDAT- 2016/05/06 06:00
MHDA- 2016/05/06 06:01
PMCR- 2016/04/18
CRDT- 2016/05/06 06:00
PHST- 2016/01/15 00:00 [received]
PHST- 2016/04/04 00:00 [accepted]
PHST- 2016/05/06 06:00 [entrez]
PHST- 2016/05/06 06:00 [pubmed]
PHST- 2016/05/06 06:01 [medline]
PHST- 2016/04/18 00:00 [pmc-release]
AID - 10.3389/fmicb.2016.00541 [doi]
PST - epublish
SO  - Front Microbiol. 2016 Apr 18;7:541. doi: 10.3389/fmicb.2016.00541. eCollection 
      2016.