Mycobacterial antigens exacerbate disease manifestations in Mycobacterium tuberculosis-infected mice

Andre L. Moreira, Liana Tsenova, Melles Haile Aman, Linda Gail Bekker, Sherry Freeman, Bande Mangaliso, Ulf Schröder, Jaishree Jagirdar, William N. Rom, Michael G. Tovey, Victoria H. Freedman, Gilla Kaplan

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Abstract

To control tuberculosis worldwide, the burden of adult pulmonary disease must be reduced. Although widely used, Mycobacterium bovis BCG vaccination given at birth does not protect against adult pulmonary disease. Therefore, postexposure vaccination of adults with mycobacterial antigens is being considered. We examined the effect of various mycobacterial antigens on mice with prior M. tuberculosis infection. Subcutaneous administration of live or heat-treated BCG with or without lipid adjuvants to infected mice induced increased antigen-specific T-cell proliferation but did not reduce the bacterial load in the lungs and caused larger lung granulomas. Similarly, additional mycobacterial antigen delivered directly to the lungs by aerosol infection with viable M. tuberculosis mixed with heat-killed Mycobacterium tuberculosis (1:1) also did not reduce the bacillary load but caused increased expression of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6), which was associated with larger granulomas in the lungs. When M. tuberculosis-infected mice were treated with recombinant BCG that secreted cytokines shown to reduce disease in a preinfection vaccine model, the BCG secreting TNF-α, and to a lesser extent, IL-2 and gamma interferon (IFN-γ), caused a significant increase in granuloma size in the lungs. Moreover, treatment of M. tuberculosis-infected mice with recombinant murine TNF-α resulted in increased inflammation in the lungs and accelerated mortality without affecting the bacillary load. Taken together, these studies suggest that administration of mycobacterial antigens to mice with prior M. tuberculosis infection leads to immune activation that may exacerbate lung pathology via TNF-α-induced inflammation without reducing the bacillary load.

Original languageEnglish (US)
Pages (from-to)2100-2107
Number of pages8
JournalInfection and Immunity
Volume70
Issue number4
DOIs
StatePublished - 2002
Externally publishedYes

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Mycobacterium tuberculosis
Mycobacterium bovis
Antigens
Lung
Tumor Necrosis Factor-alpha
Granuloma
Mycobacterium Infections
Lung Diseases
Vaccination
Hot Temperature
BCG Vaccine
Bacterial Load
Aerosols
Interferon-gamma
Interleukin-2
Interleukin-6
Pneumonia
Tuberculosis
Cell Proliferation
Parturition

ASJC Scopus subject areas

  • Immunology

Cite this

Moreira, A. L., Tsenova, L., Aman, M. H., Bekker, L. G., Freeman, S., Mangaliso, B., ... Kaplan, G. (2002). Mycobacterial antigens exacerbate disease manifestations in Mycobacterium tuberculosis-infected mice. Infection and Immunity, 70(4), 2100-2107. https://doi.org/10.1128/IAI.70.4.2100-2107.2002

Mycobacterial antigens exacerbate disease manifestations in Mycobacterium tuberculosis-infected mice. / Moreira, Andre L.; Tsenova, Liana; Aman, Melles Haile; Bekker, Linda Gail; Freeman, Sherry; Mangaliso, Bande; Schröder, Ulf; Jagirdar, Jaishree; Rom, William N.; Tovey, Michael G.; Freedman, Victoria H.; Kaplan, Gilla.

In: Infection and Immunity, Vol. 70, No. 4, 2002, p. 2100-2107.

Research output: Contribution to journalArticle

Moreira, AL, Tsenova, L, Aman, MH, Bekker, LG, Freeman, S, Mangaliso, B, Schröder, U, Jagirdar, J, Rom, WN, Tovey, MG, Freedman, VH & Kaplan, G 2002, 'Mycobacterial antigens exacerbate disease manifestations in Mycobacterium tuberculosis-infected mice', Infection and Immunity, vol. 70, no. 4, pp. 2100-2107. https://doi.org/10.1128/IAI.70.4.2100-2107.2002
Moreira, Andre L. ; Tsenova, Liana ; Aman, Melles Haile ; Bekker, Linda Gail ; Freeman, Sherry ; Mangaliso, Bande ; Schröder, Ulf ; Jagirdar, Jaishree ; Rom, William N. ; Tovey, Michael G. ; Freedman, Victoria H. ; Kaplan, Gilla. / Mycobacterial antigens exacerbate disease manifestations in Mycobacterium tuberculosis-infected mice. In: Infection and Immunity. 2002 ; Vol. 70, No. 4. pp. 2100-2107.
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