title: Constitutive expression of SMAR1 confers susceptibility to Mycobacterium tuberculosis infection in a transgenic mouse model.
abstract: OBJECTIVE
  Studies involving animal models of experimental tuberculosis have elucidated the predominant role of cytokines secreted by T cells and macrophages to be an essential component of the immune response against Mycobacterium tuberculosis infection. The immune activities of CD4+ T cells are mediated in part by Th1 cytokine interferon gamma (IFN-γ) which is produced primarily by T cells and natural killer (NK) cells and critical for initiating the immune response against intracellular pathogen such as M. tuberculosis. Nuclear matrix protein SMAR1 plays an important role in V(D)J recombination, T helper cell differentiation and inflammatory diseases. In this study a transgenic mouse model was used to study the role of SMAR1 in M. tuberculosis infection.
  
  
  METHODS
  Wild type BALB/c, C57BL/6, BALB/c-EGFP-SMAR1 and C57BL/6-SMAR1 transgenic mice were infected with M. tuberculosis (H37Rv). A dose of 100 bacilli was used for infection via respiratory route. Bacterial load in lung and spleen of infected mice was determined at 2, 4, 6 and 8 wk post-infection. Gene expression analysis for Th1 cytokines and inducible nitric oxide synthase (iNOS) was performed in infected lung tissues by quantitative reverse transcription (RT)-PCR.
  
  
  RESULTS
  SMAR1 transgenic mice from both BALB/c and C57BL/6 genetic background displayed higher bacillary load and susceptibility to M. tuberculosis infection compared to wild type mice. This susceptibility was attributed due to compromised of Th1 response exhibited by transgenic mice.
  
  
  CONCLUSIONS
  SMAR1 transgenic mice exhibited susceptibility to M. tuberculosis infection in vivo irrespective of genetic background. This susceptibility was attributed to downregulation of Th1 response and its hallmark cytokine IFN-γ. Hence, SMAR1 plays an important role in modulating host immune response after M. tuberculosis infection.
authors.forename: Bhawna
authors.initials: B
authors.lastname: Yadav
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Malonia
authors.forename: Subeer S
authors.initials: SS
authors.lastname: Majumdar
authors.forename: Pushpa
authors.initials: P
authors.lastname: Gupta
authors.forename: Neerja
authors.initials: N
authors.lastname: Wadhwa
authors.forename: Archana
authors.initials: A
authors.lastname: Badhwar
authors.forename: Umesh D
authors.initials: UD
authors.lastname: Gupta
authors.forename: Vishwa M
authors.initials: VM
authors.lastname: Katoch
authors.affiliation: National Centre for Cell Science, Pune, India.
authors.forename: Samit
authors.initials: S
authors.lastname: Chattopadhyay
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D004195:Disease Models, Animal; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000472:pathogenicity*; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D018417:Th1 Cells / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology* / Q000382:microbiology
chemical_list: C485952:Banp protein, mouse; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D007371:Interferon-gamma
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