Immunostimulatory DNA from Paracoccidioides brasiliensis acts as T-helper 1 promoter in susceptible mice

Th1 immune responses afford protection against some pathogens like the fung us R brasiliensis (P.b.), ethiological agent of Paracoccidioidomycosis (PCM ). It is well known that nonmethylated CpG sequences from bacterial DNA hav e 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 T h2 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 signif icant increase in phagocytosis when the macrophages were stimulated with DN A from Rb. and in vivo assays of a decreased production of antibodies antig p43, the main antigen of the PCM system. The analysis of the antibody isoty pes and the cytokine production suggested a Th1 modulation in the susceptib le animals. Thus, when mice were infected with fungus plus synthetic oligod eoxynucleotide (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.