Interaction of Histoplasma capsulatum with human platelets

Area of Science:

• Mycology
• Hematology
• Immunology

Background:

• Thrombocytopenia is frequently observed in disseminated histoplasmosis.
• The yeast form of Histoplasma capsulatum does not directly harm isolated human platelets.

Purpose of the Study:

• To investigate the mechanism by which Histoplasma capsulatum interacts with human platelets.
• To elucidate the role of plasma components and signaling pathways in H. capsulatum-induced platelet activation.

Main Methods:

• Platelet aggregation assays using H. capsulatum yeasts.
• Measurement of serotonin release and enzyme markers (beta-glucuronidase, lactate dehydrogenase).
• Inhibition studies using apyrase, indomethacin, and complement pathway modulators.

Main Results:

• Preincubation of H. capsulatum with plasma induced platelet aggregation and selective serotonin release.
• Platelet aggregation was mediated by adenosine diphosphate and required fibrinogen.
• Serotonin release depended on prostaglandin synthesis (inhibited by indomethacin) and was mediated by plasma IgG complexed with yeasts.
• Complement pathways were not involved.

Conclusions:

• Histoplasma capsulatum interacts with human platelets through a mechanism involving plasma IgG and fibrinogen, independent of complement.
• This interaction leads to platelet aggregation and serotonin release, potentially explaining the thrombocytopenia associated with disseminated histoplasmosis.
• This represents a novel pathogenic mechanism for H. capsulatum.