PUBLICATION

Adequate Th2-Type Response Associates with Restricted Bacterial Growth in Latent Mycobacterial Infection of Zebrafish

Authors
Hammarén, M.M., Oksanen, K.E., Nisula, H.M., Luukinen, B.V., Pesu, M., Rämet, M., Parikka, M.
ID
ZDB-PUB-140627-2
Date
2014
Source
PLoS pathogens   10: e1004190 (Journal)
Registered Authors
Keywords
Zebrafish, T cells, Mycobacterium tuberculosis, Tuberculosis, Immune response, Lymphocytes, Bacterial growth, Bacterial pathogens
MeSH Terms
  • Adaptive Immunity*
  • Algorithms
  • Animals
  • Animals, Genetically Modified
  • Bacterial Load
  • Biomarkers/blood
  • Biomarkers/metabolism
  • Disease Models, Animal*
  • Disease Progression
  • Forkhead Transcription Factors/blood
  • Forkhead Transcription Factors/genetics
  • Forkhead Transcription Factors/metabolism
  • GATA3 Transcription Factor/blood
  • GATA3 Transcription Factor/genetics
  • GATA3 Transcription Factor/metabolism
  • Gene Expression Regulation
  • Lymphocyte Count
  • Lymphopoiesis
  • Microbial Viability
  • Mutation
  • Mycobacterium Infections, Nontuberculous/blood
  • Mycobacterium Infections, Nontuberculous/immunology*
  • Mycobacterium Infections, Nontuberculous/metabolism
  • Mycobacterium Infections, Nontuberculous/microbiology
  • Mycobacterium marinum/growth & development
  • Mycobacterium marinum/immunology*
  • Mycobacterium marinum/isolation & purification
  • T-Box Domain Proteins/blood
  • T-Box Domain Proteins/genetics
  • T-Box Domain Proteins/metabolism
  • Th1 Cells/immunology
  • Th1 Cells/metabolism
  • Th1 Cells/microbiology
  • Th1 Cells/pathology
  • Th2 Cells/immunology*
  • Th2 Cells/metabolism
  • Th2 Cells/microbiology
  • Th2 Cells/pathology
  • Up-Regulation
  • Zebrafish/genetics
  • Zebrafish/immunology*
  • Zebrafish/metabolism
  • Zebrafish/microbiology
  • Zebrafish Proteins/blood
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed
24968056 Full text @ PLoS Pathog.
Abstract
Tuberculosis is still a major health problem worldwide. Currently it is not known what kind of immune responses lead to successful control and clearance of Mycobacterium tuberculosis. This gap in knowledge is reflected by the inability to develop sufficient diagnostic and therapeutic tools to fight tuberculosis. We have used the Mycobacterium marinum infection model in the adult zebrafish and taken advantage of heterogeneity of zebrafish population to dissect the characteristics of adaptive immune responses, some of which are associated with well-controlled latency or bacterial clearance while others with progressive infection. Differences in T cell responses between subpopulations were measured at the transcriptional level. It was discovered that a high total T cell level was usually associated with lower bacterial loads alongside with a T helper 2 (Th2)-type gene expression signature. At late time points, spontaneous reactivation with apparent symptoms was characterized by a low Th2/Th1 marker ratio and a substantial induction of foxp3 reflecting the level of regulatory T cells. Characteristic gata3/tbx21 has potential as a biomarker for the status of mycobacterial disease.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping