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Fungistatic activity of human neutrophils against Histoplasma capsulatum: correlation with phagocytosis
E Brummer1, N Kurita, S Yosihida
1Research Center for Pathogenic Fungi and Microbial Toxicoses, Chiba University, Japan.
Abstract:
The interaction of human polymorphonuclear leukocytes (PMNL) and Histoplasma capsulatum was studied. In limiting dilution assays and in a 2-h coculture system, PMNL were ineffective in killing H. capsulatum whereas Candida albicans was readily killed. Although PMNL could not reduce inoculum colony-forming units of H. capsulatum in short-term assays, they were highly fungistatic in 24- (47%-55%) and 72-h (65%-75%) cocultures. Phagocytosis of yeast cells by PMNL was 81.3% +/- 3.7%. Fungistasis persisted even though PMNL viability decreased with time. Fungistatic activity of PMNL was dose dependent. Fungistasis was verified by direct hemocytometer counts of fungal units. In transwell experiments, PMNL contact with H. capsulatum was required for fungistatic activity. Lymphocytes, PMNL lysates, or PMNL supernatants were not fungistatic in this system.
Insights
Human polymorphonuclear leukocytes (PMNL) inhibit Histoplasma capsulatum growth, demonstrating fungistatic, not fungicidal, activity. This interaction requires direct PMNL contact for effective control of the fungal pathogen.
Area of Science:
- Immunology
- Mycology
- Infectious Diseases
Background:
- Histoplasma capsulatum is an opportunistic fungal pathogen causing histoplasmosis.
- Polymorphonuclear leukocytes (PMNL) are crucial innate immune cells involved in pathogen clearance.
Purpose of the Study:
- To investigate the interaction between human PMNL and Histoplasma capsulatum.
- To determine the fungicidal and fungistatic capabilities of PMNL against H. capsulatum.
Main Methods:
- Coculture assays (2-h, 24-h, 72-h) with H. capsulatum and human PMNL.
- Limiting dilution assays and transwell experiments.
- Direct hemocytometer counts for fungal viability assessment.
- Phagocytosis assays.
Main Results:
- PMNL showed limited fungicidal activity against H. capsulatum in short-term assays.
- Significant PMNL fungistasis (47%-75%) was observed in longer cocultures (24-h, 72-h).
- High phagocytosis rates (81.3%) were noted, but fungistasis persisted despite PMNL viability decline.
- Direct cell contact between PMNL and H. capsulatum was essential for fungistatic effect.
Conclusions:
- Human PMNL exhibit potent fungistatic activity against Histoplasma capsulatum.
- The fungistatic effect is dose-dependent and requires direct PMNL-fungal contact.
- PMNL play a significant role in controlling H. capsulatum infection through growth inhibition rather than direct killing.