Immunostimulatory DNA from Paracoccidioides brasiliensis acts as T-helper 1 promoter in susceptible mice
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2001-10-01
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Th1 immune responses afford protection against some pathogens like the fungus R brasiliensis (P.b.), ethiological agent of Paracoccidioidomycosis (PCM). It is well known that nonmethylated CpG sequences from bacterial DNA have immunomodulatory properties and can be used as a Th1-promoting adjuvant. By analyzing the available gene sequences of P.b. we observed a high number of unmethylated CpG dinucleotides. in a murine model of the PCM infection, the isogenic mouse strain known to be susceptible presents a predominant Th2 pattern. in order to access the possibility of the genomic DNA to act as a Th1-promoting adjuvant, in vitro assays were made and indicated a significant increase in phagocytosis when the macrophages were stimulated with DNA from Rb. and in vivo assays of a decreased production of antibodies antigp43, the main antigen of the PCM system. the analysis of the antibody isotypes and the cytokine production suggested a Th1 modulation in the susceptible animals. Thus, when mice were infected with fungus plus synthetic oligodeoxynucleotide (ODN), made from the available sequence of gp43, a decrease in the fungus dissemination was observed. Results herein described suggest that genomic DNA from Rb. could have a immunostimulatory function as a Th-1-promoting adjuvant in susceptible mice.
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Scandinavian Journal of Immunology. Oxford: Blackwell Science Ltd, v. 54, n. 4, p. 348-356, 2001.