Abstract
Paracoccidioidomycosis (PCM), endemic in Latin America, is a progressive systemic mycosis caused by Paracoccidioides brasiliensis (P. brasiliensis), which primarily attacks lung tissue. Dendritic cells (DCs) are able to initiate a response in naïve T cells, and they also participate in Th-cell education. Furthermore, these cells have been used for therapy in several disease models. Here we transfected DCs with a plasmid (pMAC/PS-scFv) encoding a single chain variable fragment (scFv) of an anti-Id antibody that is capable of mimicking gp43, the main antigenic component of P. brasiliensis. First, Balb/c mice were immunized subcutaneously with pMAC/PS-scFv and, after seven days, scFv protein was presented to the regional lymph nodes cells. Moreover, we showed that the DCs transfected with scFv were capable of efficiently activating proliferation of total lymph node cells and inducing a decrease in lung infection. Therefore, our results suggested that the use of scFv-transfected DCs may be a promising therapy in the paracoccidioidomycosis (PCM) model.
Highlights
Paracoccidioidomycosis (PCM) is a mycotic disease caused by a terminally dimorphic fungus Paracoccidioides brasiliensis (P. brasiliensis), which initiates a deep mycosis and a primary attack on the lung tissue
Based on the knowledge that a conversion to IgG4 is dependent on interleukin-4 and that the conversion to IgG2 is influenced by interferon-c [5,6], it is suggested that the sub-acute form is related to a Th2-type pattern of immune response, while a chronic form is related to a protective response (Th1-type) in the PCM disease
The scFv gene was transferred to the pMAC/PS vector so that it could be expressed in mammalian cells
Summary
Paracoccidioidomycosis (PCM) is a mycotic disease caused by a terminally dimorphic fungus Paracoccidioides brasiliensis (P. brasiliensis), which initiates a deep mycosis and a primary attack on the lung tissue. The main antigenic component of the P. brasiliensis is a 43-kDa glycoprotein that has been shown to elicit strong antibody and cellular immune responses in human and experimental models [2,3]. Antibodies against this glycoprotein can be detected during all stages of the disease. Based on the knowledge that a conversion to IgG4 is dependent on interleukin-4 and that the conversion to IgG2 is influenced by interferon-c [5,6], it is suggested that the sub-acute form is related to a Th2-type pattern of immune response, while a chronic form is related to a protective response (Th1-type) in the PCM disease
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