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A Paracoccidioides brasiliensis polysaccharide having granuloma-inducing, toxic and macrophage-stimulating activity
Abstract:
The occurrence of a polysaccharide fraction of Paracoccidioides brasiliensis cell wall with toxic, granuloma-inducing and macrophage-stimulating activities was demonstrated. After fractionation of the lipid-extracted wall with 1 M-NaOH, three fractions were obtained: (1) an alkali-insoluble fraction; (2) an alkali-soluble, acid-insoluble fraction and (3) an alkali-soluble, acid-soluble fraction. When the three fractions were injected into mice only fraction (1) was able to induce chronic lung inflammation, causing a marked loss in body weight and death at a dose of 6 mg per animal. Analysis of the stimulation of peritoneal macrophages of mice (measured by cell spreading on glass) after intraperitoneal injection of fraction 1 showed that 75% of the cells were able to spread even 20 d after inoculation.
Insights
A toxic polysaccharide fraction from the Paracoccidioides brasiliensis cell wall induced lung inflammation and stimulated macrophages in mice. This fraction demonstrated significant toxicity, causing weight loss and death.
Area of Science:
- Immunology
- Mycology
- Pathology
Background:
- The cell wall of Paracoccidioides brasiliensis contains biologically active components.
- Understanding the immunomodulatory properties of fungal cell wall polysaccharides is crucial for disease management.
Purpose of the Study:
- To isolate and characterize polysaccharide fractions from the Paracoccidioides brasiliensis cell wall.
- To evaluate the toxic, granuloma-inducing, and macrophage-stimulating activities of these fractions in a murine model.
Main Methods:
- Lipid extraction of the Paracoccidioides brasiliensis cell wall followed by fractionation using 1 M-NaOH.
- Injection of isolated fractions into mice to assess toxicity and inflammatory responses.
- Analysis of peritoneal macrophage stimulation by measuring cell spreading.
Main Results:
- Three distinct polysaccharide fractions were obtained: alkali-insoluble, alkali-soluble/acid-insoluble, and alkali-soluble/acid-soluble.
- The alkali-insoluble fraction induced chronic lung inflammation, significant weight loss, and mortality in mice at 6 mg/animal.
- This fraction also demonstrated potent macrophage-stimulating activity, with 75% of peritoneal macrophages spreading 20 days post-inoculation.
Conclusions:
- A specific polysaccharide fraction of the Paracoccidioides brasiliensis cell wall possesses significant toxicity and potent immunomodulatory effects.
- The alkali-insoluble fraction is responsible for the observed lung inflammation and macrophage activation, highlighting its role in Paracoccidioidomycosis pathogenesis.