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Bacillus Calmette-Guérin sequestered in the brain parenchyma escapes immune recognition
Malgosia K Matyszak1, V Hugh Perry1
1CNS Inflammation Group, University Department of Pharmacology, University of Oxford, Mansfield Rd., Oxford OX1 3QT, UK.
Abstract:
We have previously shown that heat-killed bacillus Calmette-Guérin (BCG) injected into the brain parenchyma becomes sequestered behind the blood-brain barrier for months, apparently unrecognised by the immune system (Matyszak and Perry, 1995, 1996a,b). In this paper we have studied T-cell and antibody responses to purified protein derivative (PPD) at different times after intracranial injection of BCG or after the same dose of BCG was injected intradermally. We detected no antibody to PPD in the sera of animals which received intracranial injection, although there was a clear antibody response in the sera of animals injected intradermally, as shown using immunoblot analysis. The skin contact sensitivity to PPD was robust in animals which had received a previous intradermal injection of BCG. 72 h after a PPD injection, the injected site showed many MHC class II + macrophages and T-cells. However, the response in skin following PPD challenge, in animals injected intracranially (i.c.), was comparable with that of naive animals which had received no previous BCG challenge. The skin lesions in animals injected i.c. and in naive animals, were characterised by a small number of MHC class II + cells and rare T-cells. T-cell responses were also studied in an in vitro proliferation assay. The proliferative response was measured for cells isolated from the cervical lymph nodes and the spleen. Cells purified from the spleen and the cervical lymph nodes of animals injected with BCG i.c. showed no specific proliferative response to PPD. The response was comparable to that found in naive, uninjected animals. However, spleen and cervical lymph node cells from animals injected intradermally with BCG showed a significant proliferative response to PPD. These results show that a dose of bacteria injected into the brain parenchyma fails to prime the immune system even though the same dose injected subcutaneously will do so. This response to bacteria in the CNS differs from that previously reported for soluble proteins.
Insights
Intracranial injection of heat-killed bacillus Calmette-Guérin (BCG) does not prime the immune system, unlike intradermal BCG administration. This indicates the central nervous system (CNS) immune response differs from peripheral responses to bacteria.
Area of Science:
- Neuroimmunology
- Immunology
- Microbiology
Background:
- Heat-killed bacillus Calmette-Guérin (BCG) injected into the brain parenchyma is sequestered behind the blood-brain barrier.
- The immune system appears to not recognize BCG within the brain parenchyma.
Purpose of the Study:
- To investigate T-cell and antibody responses to purified protein derivative (PPD) after intracranial versus intradermal BCG injection.
- To compare immune priming in the central nervous system (CNS) versus peripheral sites.
Main Methods:
- Animals received either intracranial or intradermal BCG injections.
- Antibody responses were assessed via immunoblot analysis.
- Skin contact sensitivity to PPD was evaluated.
- T-cell proliferation assays were performed on cells from spleen and lymph nodes.
Main Results:
- No antibodies to PPD were detected in sera after intracranial BCG injection, unlike intradermal injection.
- Skin contact sensitivity to PPD was absent after intracranial BCG, but robust after intradermal BCG.
- T-cells from spleen and lymph nodes showed no proliferative response to PPD after intracranial BCG, but a significant response after intradermal BCG.
Conclusions:
- A dose of BCG injected into the brain parenchyma fails to prime the immune system.
- Immune responses to bacteria in the CNS differ from those in the periphery and from responses to soluble proteins.