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- Arko-Mensah, John, et al.
(author)
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Increased levels of immunological markers in the respiratory tract but not in serum correlate with active pulmonary mycobacterial infection in mice
- 2009
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In: Clinical Microbiology and Infection. - : Elsevier BV. - 1198-743X .- 1469-0691. ; 15:8, s. 777-786
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Journal article (peer-reviewed)abstract
- Immunological tests for the diagnosis of tuberculosis (TB) have relied mostly on detection of immune markers in serum or release of cytokines by mononuclear cells in vitro. These tests, although useful, sometimes fail to discriminate between active infection and contact with mycobacteria or vaccination. TB is primarily a disease of the lung, and therefore identification of immunological markers in the respiratory tract will be more likely to reflect the infection status or disease activity. In this study, it is demonstrated that active infection of mice with Mycobacterium bovis bacille Calmette-Guérin (BCG), but not exposure to heat-killed BCG, induced production of interleukin-12 (IL-12), interferon-gamma (IFN-gamma) or soluble tumour necrosis factor receptors (sTNFRs) locally in the lungs, as detected in bronchoalveolar lavage (BAL) fluid. There was a strong correlation between bacterial growth in the lung and levels of sTNFRs, and to some extent IL-12 and IFN-gamma, in BAL fluid. Furthermore, sTNFR levels increased significantly in BAL fluid after reactivation of controlled infection with dexamethasone, and this correlated with increased bacterial growth in the lungs. Finally, infection, but not exposure to non-replicating mycobacteria, induced specific IgG and IgA in BAL fluid. Elevated levels of all biomarkers measured were also detected in the serum, but correlation with infection was not as clear as in the case of BAL fluid. Taken together, the detection of sTNFRs and mycobacterium-specific antibodies, especially IgA, locally in the lungs could be used as immunological markers for the diagnosis of TB.
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| 2. |
- Arko-Mensah, John, et al.
(author)
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Resistance to mycobacterial infection : a pattern of early immune responses leads to a better control of pulmonary infection in C57BL/6 compared with BALB/c mice.
- 2009
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In: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 27:52, s. 7418-27
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Journal article (peer-reviewed)abstract
- In this study, we have compared the immunological responses associated with early pulmonary mycobacterial infection in two mouse strains, BALB/c and C57BL/6 known to exhibit distinct differences in susceptibility to infection with several pathogens. We infected mice via the intranasal route. We have demonstrated that BALB/c was less able to control mycobacterial growth in the lungs during the early phase of pulmonary infection. Our results showed that during the early phase (day 3 to week 1), BALB/c mice exhibited a delay in the production of TNF and IFN-gamma in the lungs compared to C57BL/6 mice. Levels of IL-12 and soluble TNF receptors (sTNFR) were comparable between the mouse strains. The cellular subset distribution in these mice before and after infection showed a higher increase in CD11b+ cells in the lungs of C57BL/6, compared to BALB/c as early as day 3 postinfection. At early time points, higher levels of monocyte chemoattractant protein (MCP)-1 and macrophage inflammatory protein 1 (MIP)-alpha were detected in C57BL/6 than BALB/c mice. In vitro, BCG-infected bone marrow derived macrophages (BMM) from both mouse strains displayed similar capacities to either phagocytose bacteria or produce soluble mediators such as TNF, IL-12 and nitric oxide (NO). Although IFN-gamma stimulation of infected BMM in both mouse strains resulted in the induction of antimycobacterial activity, BALB/c mice had a reduced capacity to kill ingested bacteria. The above observations indicate that the chain of early, possibly innate immunological events occurring during pulmonary mycobacterial infection may directly impact on increased susceptibility or resistance to infection.
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