Related Experiment Videos
Coccidioidomycosis: factors affecting the host-parasite interaction
Abstract:
The inhaled arthroconidia of Coccidioides immitis mature to form large (30-80 micron) endosporulating spherules. Each spherule releases hundreds of endospores, taxing immunologic reserves. Polymorphonuclear neutrophils (PMNs) are prominent in the lesions of coccidioidomycosis, but their effectiveness is questionable. Arthroconidia possess an antiphagocytic surface derived from the original hyphal outer wall layer. Only 20%-30% of arthroconidia or endospores that are ingested by PMNs are killed. PMNs can digest the outer wall layer of spherules but may not induce lethal injury. Cell-mediated immunity is central to host defense. Macrophages ingest arthroconidia and endospores but may be unable to kill them unless lymphokines stimulate phagolysosomal fusion. Whether spherules can be killed by macrophages is unclear. C. immitis is stimulated directly by serum levels of estradiol and progesterone achieved in pregnant women. This, together with the depressed cell-mediated immunity of pregnancy, may account for the virulent nature of coccidioidomycosis in pregnant women.
Insights
Coccidioides immitis spherules release endospores, challenging immune responses. Polymorphonuclear neutrophils and macrophages struggle to eliminate fungal forms, especially during pregnancy due to hormonal influences and reduced cell-mediated immunity.
Area of Science:
- Mycology
- Immunology
- Infectious Diseases
Background:
- Coccidioides immitis forms spherules that release endospores, overwhelming host defenses.
- Polymorphonuclear neutrophils (PMNs) are present in coccidioidomycosis lesions but have limited efficacy.
- Cell-mediated immunity is crucial for controlling Coccidioides immitis infections.
Purpose of the Study:
- To investigate the interactions between Coccidioides immitis fungal forms and host immune cells.
- To understand the limitations of innate and cell-mediated immunity in combating Coccidioides immitis.
- To explore factors contributing to severe coccidioidomycosis in pregnant women.
Main Methods:
- Analysis of arthroconidia and spherule morphology and release of endospores.
- Evaluation of Polymorphonuclear neutrophil (PMN) phagocytosis and killing of fungal elements.
- Assessment of macrophage interaction with Coccidioides immitis, including the role of lymphokines.
- Correlation of Coccidioides immitis growth with hormone levels in pregnant women.
Main Results:
- Arthroconidia have an antiphagocytic surface, with only 20-30% killed by PMNs.
- PMNs can damage spherules but may not achieve lethal injury.
- Macrophages require lymphokine stimulation for effective killing of fungal forms; spherule killing by macrophages is uncertain.
- Estradiol and progesterone stimulate C. immitis, potentially exacerbating infection during pregnancy due to suppressed cell-mediated immunity.
Conclusions:
- The immune system, including PMNs and macrophages, has limited effectiveness against Coccidioides immitis fungal forms.
- Hormonal fluctuations and reduced cell-mediated immunity during pregnancy significantly increase the virulence of coccidioidomycosis.
- Further research is needed to elucidate macrophage mechanisms against spherules and develop targeted therapies.