T helper 1-inducing adjuvant protects against experimental paracoccidioidomycosis.
Immunostimulatory therapy is a promising approach to improving the treatment of systemic fungal infections such as paracoccidioidomycosis (PCM), whose drug therapy is usually prolonged and associated with toxic side effects and relapses. The current study was undertaken to determine if the injection of a T helper (Th) 1-stimulating adjuvant in P. brasiliensis-infected mice could have a beneficial effect on the course of experimental PCM. For this purpose, mice were infected and treated with complete Freund's adjuvant (CFA), a well-established Th1 experimental inductor, or incomplete Freund's adjuvant (IFA - control group) on day 20 postinfection. Four weeks after treatment, the CFA-treated mice presented a mild infection in the lungs characterized by absence of epithelioid cell granulomas and yeast cells, whereas the control mice presented multiple sites of focal epithelioid granulomas with lymphomonocytic halos circumscribing a high number of viable and nonviable yeast cells. In addition, CFA administration induced a 2.4 log reduction (>99%) in the fungal burden when compared to the control group, and led to an improvement of immune response, reversing the immunosuppression observed in the control group. The immunotherapy with Th1-inducing adjuvant, approved to be used in humans, might be a valuable tool in the treatment of PCM and potentially useful to improve the clinical cure rate in humans.
de Oliveira
Leandro Licursi
LL
Department of Cellular and Molecular Biology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Coltri
Kely Cristine
KC
Cardoso
Cristina Ribeiro Barros
CR
Roque-Barreira
Maria-Cristina
MC
Panunto-Castelo
Ademilson
A
D000818:Animals; D000946:Antigens, Fungal / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005620:Freund's Adjuvant / Q000494:pharmacology / Q000627:therapeutic use*; D066298:In Vitro Techniques; D008055:Lipids / Q000494:pharmacology / Q000627:therapeutic use*; D008168:Lung / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010228:Paracoccidioides / Q000276:immunology*; D010229:Paracoccidioidomycosis / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D013234:Stem Cells; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology*
D000946:Antigens, Fungal; D008055:Lipids; C114843:incomplete Freund's adjuvant; D005620:Freund's Adjuvant