PMID- 27763806
OWN - NLM
STAT- MEDLINE
DCOM- 20180522
LR  - 20240327
IS  - 2150-5608 (Electronic)
IS  - 2150-5594 (Print)
IS  - 2150-5594 (Linking)
VI  - 8
IP  - 6
DP  - 2017 Aug 18
TI  - RNAseq reveals hypervirulence-specific host responses to M. tuberculosis 
      infection.
PG  - 848-858
LID - 10.1080/21505594.2016.1250994 [doi]
AB  - The distinguishing factors that characterize the host response to infection with 
      virulent Mycobacterium tuberculosis (M.tb) are largely confounding. We present an 
      infection study with 2 genetically closely related M.tb strains that have vastly 
      different pathogenic characteristics. The early host response to infection with 
      these detergent-free cultured strains was analyzed through RNAseq in an attempt 
      to provide information on the subtleties which may ultimately contribute to the 
      virulent phenotype. Murine bone marrow derived macrophages (BMDMs) were infected 
      with either a hyper- (R5527) or hypovirulent (R1507) Beijing M. tuberculosis 
      clinical isolate. RNAseq revealed 69 differentially expressed host genes in BMDMs 
      during comparison of these 2 transcriptomes. Pathway analysis revealed activation 
      of the stress-induced and growth inhibitory Gadd45 signaling pathway in 
      hypervirulent infected BMDMs. Upstream regulators of interferon activation such 
      as and IRF3 and IRF7 were predicted to be upregulated in hypovirulent-infected 
      BMDMs. Additional analysis of the host immune response through ELISA and qPCR 
      included the use of human THP-1 macrophages where a robust proinflammatory 
      response was observed after infection with the hypervirulent strain. RNAseq 
      revealed 2 early-response genes (ier3 and saa3) and 2 host-defense genes (oasl1 
      and slpi) that were significantly upregulated by the hypervirulent strain. The 
      role of these genes under M.tb infection conditions are largely unknown but here 
      we provide validation of their presence with use of qPCR and Western blot. 
      Further analysis into their biological role during infection with virulent M.tb 
      is required.
FAU - Leisching, Gina
AU  - Leisching G
AUID- ORCID: 0000-0002-4764-4781
AD  - a SA MRC Center for TB Research , DST/NRF Center of Excellence for Biomedical 
      Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty 
      of Medicine and Health Sciences, Stellenbosch University , Tygerberg , South 
      Africa.
FAU - Pietersen, Ray-Dean
AU  - Pietersen RD
AD  - a SA MRC Center for TB Research , DST/NRF Center of Excellence for Biomedical 
      Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty 
      of Medicine and Health Sciences, Stellenbosch University , Tygerberg , South 
      Africa.
FAU - van Heerden, Carel
AU  - van Heerden C
AD  - b Central Analytical Facility (CAF) , DNA Sequencing Unit, Stellenbosch 
      University , Stellenbosch , South Africa.
FAU - van Helden, Paul
AU  - van Helden P
AD  - a SA MRC Center for TB Research , DST/NRF Center of Excellence for Biomedical 
      Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty 
      of Medicine and Health Sciences, Stellenbosch University , Tygerberg , South 
      Africa.
FAU - Wiid, Ian
AU  - Wiid I
AD  - a SA MRC Center for TB Research , DST/NRF Center of Excellence for Biomedical 
      Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty 
      of Medicine and Health Sciences, Stellenbosch University , Tygerberg , South 
      Africa.
FAU - Baker, Bienyameen
AU  - Baker B
AD  - a SA MRC Center for TB Research , DST/NRF Center of Excellence for Biomedical 
      Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty 
      of Medicine and Health Sciences, Stellenbosch University , Tygerberg , South 
      Africa.
LA  - eng
PT  - Journal Article
DEP - 20161020
PL  - United States
TA  - Virulence
JT  - Virulence
JID - 101531386
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Gadd45a protein, mouse)
RN  - 0 (Interferon Regulatory Factor-3)
RN  - 0 (Interferon Regulatory Factor-7)
RN  - 0 (Irf3 protein, mouse)
RN  - 0 (Irf7 protein, mouse)
RN  - 0 (Nuclear Proteins)
SB  - IM
CIN - Virulence. 2017 Aug 18;8(6):632-634. PMID: 27820666
MH  - Animals
MH  - Blotting, Western
MH  - Cell Cycle Proteins/genetics
MH  - Gene Expression Profiling
MH  - High-Throughput Nucleotide Sequencing
MH  - *Host-Pathogen Interactions
MH  - Humans
MH  - Interferon Regulatory Factor-3/genetics
MH  - Interferon Regulatory Factor-7/genetics
MH  - Macrophages/microbiology
MH  - Mice
MH  - Mycobacterium tuberculosis/genetics/immunology/*pathogenicity
MH  - Nuclear Proteins/genetics
MH  - Real-Time Polymerase Chain Reaction
MH  - Signal Transduction
MH  - Tuberculosis/*microbiology
MH  - Virulence
PMC - PMC5626229
OTO - NOTNLM
OT  - RNAseq
OT  - host-response
OT  - infection
OT  - mycobacterium tuberculosis
OT  - virulence
EDAT- 2016/10/21 06:00
MHDA- 2018/05/23 06:00
PMCR- 2016/10/20
CRDT- 2016/10/21 06:00
PHST- 2016/10/21 06:00 [pubmed]
PHST- 2018/05/23 06:00 [medline]
PHST- 2016/10/21 06:00 [entrez]
PHST- 2016/10/20 00:00 [pmc-release]
AID - 1250994 [pii]
AID - 10.1080/21505594.2016.1250994 [doi]
PST - ppublish
SO  - Virulence. 2017 Aug 18;8(6):848-858. doi: 10.1080/21505594.2016.1250994. Epub 
      2016 Oct 20.