Coccidioidomycosis: factors affecting the host-parasite interaction.

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.