Characteristics of Paecilomyces lilacinus infection comparing immunocompetent with immunosuppressed murine model

Abstract

The characteristics of Paecilomyces lilacinus infection were evaluated using two murine experimental models: immunocompetent and immunosuppressed. The evaluation criteria for characteristics of infection were clinical signs, weight loss, survival rates, histopathological alterations and the number of viable fungal cells re-isolated from different organs; and those for immunological status were in vitro lymphoproliferative response, cell surface phenotyping and IFN-γ production. Morphological evaluation showed that P. lilacinus isolates presented morphological characteristics consistent with those described in the literature. The immunocompetent mice could be infected by the fungi, but they did not develop the disease, unlike the immunosuppressed mice, which showed clinical signs of mycosis in an environment of suppressed cellular immune response. The hypothesis of latent infection reactivation in mice was not confirmed. The difference observed in the infection rate of the two fungi isolates points to an intrinsic variation between strains of P. lilacinus and led us to hypothesise that even in the presence of immunosuppressed environment, the fungus virulence can play a role in the pathogenesis of hyalohyphomycosis.

Experimental Hyalohyphomycosis by Purpureocillium lilacinum: Outcome of the Infection in C57BL/6 Murine Models

“…Some characteristics, as immunosuppression, increase the ability of a pathogen to infect a host, and according to Casadevall et al (2011) , infection is a condition for virulence. Our results corroborate those authors statement since experimental host immunosuppression was necessary to provoke hyalohyphomycosis clinical signs by P. lilacinum in C57BL/6 murine model as well as in BALB/c mice studied by Brito et al (2011) .…”

“…Some authors described the necessity of a high inoculum—10 6 to 10 8 conidia—and immunosuppression to produce an established experimental infection with P. lilacinum ( Pujol et al, 2002 ; Pastor and Guarro, 2006 ). However, Brito et al (2011) using an inoculum of 10 4 conidia were able to produce infection and disease in competent and immunosuppressed BALB/c models by the intravenous route similar to the infection caused in the C57BL/6 model used here. Although C57BL/6 mice are described as more resistant to some microorganisms, for example, Leishmania spp.…”

“…To perform immunosuppression mice received 5 mg/kg of dexamethasone (Hypofarma, Ribeirão das Neves, Brazil) administered ad libitum in the drinking water for 3 days before fungal inoculation and during all the experiments ( Brito et al, 2011 ). Tetracycline (1000 mg/L, Teuto, São Paulo, Brazil) was also added to the drinking water in parallel in order to prevent bacterial infections.…”

“…The virulence of P. lilacinum has been considered moderate by some authors and in experimental models it has been reported as low and requiring high inocula along with immunosuppression of the animals to establish infection ( Pujol et al, 2002 ; Pastor and Guarro, 2006 ). However, our group showed the ability of this fungus to infect and cause disease in immunocompetent and immunosuppressed BALB/c mice with low inoculums ( Brito et al, 2011 ).…”

“…Studies using animal models may demonstrate how fungi invade human bodies, the conditions that change fungal morphology and physiology, as well as an understanding the real mechanism of host defense ( Pujol et al, 2002 ; Brito et al, 2011 ). Our group, exploring the in vitro interaction between peritoneal macrophages from C57BL/6 mice and P. lilacinum isolates, showed that conidia adhered to mammal cells were internalized and produced germ tube and mycelium ( Peixoto et al, 2010 ).…”