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Biologically active components from mycobacterial cell walls. III. Production of experimental allergic
Abstract:
The efficacy of various fractions of mycobacterial cell walls in producing experimental ahlergic encephalomyelitis (EAE) has been evaluated. BCG (Bacillus-Calmette-Buérin) cell walls were effective in producing EAE in all animals at dose levels as low as 40 mug. Study of subfractions of these cell walls revealed the following: (1) wax D was active, but required larger doses than BCG cell walls; (2) the chloroform-methanol-soluble (CMS) portion of wax D and P3 (a mycolic acid-trehalose ester contained therein) were inactive; (3) the chloroform-methanol-insoluble (CMI) portion of wax D was active; (4) exhaustively delipidated cell wass skeletons of BCG, Nocardia asteroides, Mycobacterium smegmatis, Corynebacterium diphtheriae and M. kansaii were active; (5) two water-soluble adjuvants prepared from mycobacteria were active. These results suggest that the mycobacterial structure responsible for EAE adjuvanticity is present in the organic solvent-insoluble cell wall skeleton framework. The activity of wax D may be due to the presence of cell-wall skeleton constituents which are found in varying quanity in most wax D preparations. Wax D components soluble in a solution of chloroform:methanol (diluted 2:1 v/v) do not produce EAE.
Insights
Mycobacterial cell walls, particularly Bacillus-Calmette-Buérin (BCG), effectively induce experimental allergic encephalomyelitis (EAE). The active component resides in the organic solvent-insoluble cell wall skeleton framework, not lipid-soluble fractions.
Area of Science:
- Immunology
- Microbiology
- Neuroscience
Background:
- Experimental allergic encephalomyelitis (EAE) is an animal model for multiple sclerosis.
- Mycobacterial cell walls are known for their adjuvant properties.
- Understanding the specific components responsible for EAE induction is crucial for developing targeted therapies.
Purpose of the Study:
- To evaluate the efficacy of different mycobacterial cell wall fractions in inducing EAE.
- To identify the specific structural components of mycobacteria responsible for EAE adjuvanticity.
Main Methods:
- Fractionation of Bacillus-Calmette-Buérin (BCG) cell walls.
- Testing various subfractions, including wax D, chloroform-methanol-soluble (CMS), and chloroform-methanol-insoluble (CMI) portions.
- Assessing the EAE-inducing capacity of delipidated cell wall skeletons from various mycobacteria species.
- Evaluating water-soluble adjuvants derived from mycobacteria.
Main Results:
- BCG cell walls were potent inducers of EAE.
- Wax D showed activity, but required higher doses than whole BCG cell walls.
- The CMI portion of wax D was active, while the CMS portion and P3 were inactive.
- Delipidated cell wall skeletons from BCG, Nocardia asteroides, Mycobacterium smegmatis, Corynebacterium diphtheriae, and M. kansaii demonstrated EAE-inducing activity.
- Water-soluble mycobacterial adjuvants also exhibited activity.
Conclusions:
- The mycobacterial structure responsible for EAE adjuvanticity is located within the organic solvent-insoluble cell wall skeleton framework.
- The activity of wax D is likely attributed to the presence of these cell-wall skeleton constituents.
- Lipid-soluble components of wax D do not induce EAE.