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Influence of fungal surface components on the interaction of Coccidioides immitis with polymorphonuclear neutrophils
Abstract:
Polymorphonuclear neutrophils (PMNs) possess phagocytic and fungicidal activity against Coccidioides immitis that declines during maturation from arthroconidia to round cells, is lost throughout spherule maturation, and returns when endospores are released from ruptured spherules. Studies of PMN chemiluminescence, iodination, and degranulation give similar results. Phagocytosis of forms other than spherules is strain dependent and enhanced by immune serum. The absence of adequate PMN-spherule interaction may be attributed to the production of an extracellular fibrillar matrix, glycoprotein in composition, that restricts intimate PMN-spherule contact. When the spherule ruptures, PMNs enter to phagocytose endospores that are themselves invested by a matrix derived from the inner spherule wall. The immunochemical relationship between the outer matrix and the inner matrix remains to be discovered. Nevertheless, presence of the outer matrix may help to explain the long-standing histopathologic observation that PMNs fail to attack spherules until they release their endospores.
Insights
Polymorphonuclear neutrophils (PMNs) show reduced activity against Coccidioides immitis during fungal maturation. An extracellular matrix likely hinders PMN interaction with fungal spherules, impacting immune response.
Area of Science:
- Medical Mycology
- Immunology
- Cell Biology
Background:
- Polymorphonuclear neutrophils (PMNs) are crucial for fighting fungal infections like Coccidioides immitis.
- The interaction between PMNs and C. immitis is complex and varies with the fungal developmental stage.
Purpose of the Study:
- To investigate the phagocytic and fungicidal activity of PMNs against different forms of C. immitis.
- To elucidate the mechanisms underlying PMN-fungal interactions, particularly the role of extracellular matrices.
Main Methods:
- Assays measuring PMN functions including phagocytosis, chemiluminescence, iodination, and degranulation.
- Microscopic observation of PMN-fungal interactions.
- Analysis of fungal extracellular matrix composition.
Main Results:
- PMN activity against C. immitis declines during arthroconidia and spherule maturation but recovers upon endospore release.
- Phagocytosis is strain-dependent and enhanced by immune serum.
- An extracellular fibrillar glycoprotein matrix on spherules restricts PMN contact, explaining delayed PMN attack.
Conclusions:
- The extracellular matrix produced by C. immitis spherules is a key factor limiting PMN-mediated clearance.
- Understanding these interactions is vital for developing effective therapeutic strategies against coccidioidomycosis.