Experimental coccidioidomycosis in the immunosuppressed rat

Area of Science:

• Immunology
• Mycology
• Infectious Diseases

Background:

• Coccidioides immitis (C. immitis) infection in rats typically remains localized to the lungs.
• Cyclophosphamide (CY) treatment, however, causes dissemination of C. immitis and increases mortality.
• The underlying mechanisms for CY-induced dissemination are not fully understood.

Purpose of the Study:

• To elucidate the immunological mechanisms behind C. immitis dissemination following cyclophosphamide (CY) treatment.
• To investigate the role of T cell subpopulations in the host response to disseminated C. immitis infection under immunosuppression.

Main Methods:

• Transfer of spleen cells from infected, CY-treated rats to infected, untreated rats.
• Assessment of footpad swelling response to coccidioidin as a measure of cellular immunity.
• Evaluation of Natural Killer (NK) cell activity.
• Quantification of C. immitis colony-forming units (CFUs) in chronically infected rats receiving CY.

Main Results:

• Spleen cell transfer from CY-treated donors significantly inhibited footpad swelling in recipients, indicating the induction of suppressor T cells.
• These suppressor T cells are attributed to heightened fungal antigen concentration from disseminated C. immitis in immunosuppressed hosts.
• Natural Killer (NK) cell activity remained comparable between CY-treated and untreated rats.
• Chronically infected rats receiving weekly CY doses showed increased C. immitis CFU counts.

Conclusions:

• Cyclophosphamide (CY) treatment induces a suppressor T cell subpopulation in C. immitis-infected rats, promoting fungal dissemination.
• The induction of suppressor T cells is linked to increased fungal antigen load in immunosuppressed hosts.
• These findings have implications for understanding C. immitis behavior in immunosuppressed patients with pre-existing infections.