PMID- 16253119 OWN - NLM STAT- MEDLINE DCOM- 20051207 LR - 20061115 IS - 0300-9475 (Print) IS - 0300-9475 (Linking) VI - 62 IP - 4 DP - 2005 Oct TI - Adjuvant effect of synthetic oligodeoxyribonucleotides (CpG-ODN) from the Paracoccidioides brasiliensis gp43 gene on the Th2-Th1 immunomodulation of experimental paracoccidioidomycosis. PG - 325-33 AB - Paracoccidioidomycosis (PCM) is caused by the dimorphic fungus Paracoccidioides brasiliensis. Immunostimulatory effects of P. brasiliensis DNA and CpG-oligodeoxyribonucleotides (CpG-ODN) have shown a Th2-Th1 immunomodulation of the isogenic murine model of susceptibility, which develops a progressive and disseminating disease. In this study, we investigated the optimum time interval and doses of CpG-ODN which are able to induce Th2-Th1 immunomodulation. The optimum concentrations for the induction of a decrease in antibody production were 0.5 and 1 microg. Mice immunized twice with CpG-ODN and gp43 (5 and 7 days before the challenge) showed a 60% higher chance of survival compared with the control group (nonimmunized), and an increase in Th1 isotype (IgG2a) was also observed. In vitro assays of naive and preimmunized mice showed discrete cellular proliferation when stimulated by suitable concentrations of CpG-ODN. Type 1 cytokines interleukin-12 (IL-12) and interferon-gamma were increased in cell culture supernatants, but no significant difference was found in Th2 IL-4 cytokines in stimulated or nonstimulated cell cultures. Concerning the Th2-Th1 kinetics in experimental PCM models by adjuvant effect of CpG-ODN, there are still many questions to be answered and clarified. However, the gathering of data obtained in this investigation has led us to suggest that the modulation of Th2-Th1 in experimental PCM depends on time and CpG-ODN concentration. FAU - Amaral, C C AU - Amaral CC AD - Discipline of Cellular Biology, Department of Microbiology, Immunology and Parasitology, Federal University of Sao Paulo, Brazil. FAU - Garcia, I P AU - Garcia IP FAU - Fernandes, G F AU - Fernandes GF FAU - Almeida, S R AU - Almeida SR FAU - Camargo, Z P AU - Camargo ZP FAU - Souza, M C AU - Souza MC LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Scand J Immunol JT - Scandinavian journal of immunology JID - 0323767 RN - 0 (43 kDa protein, Paracoccidioides) RN - 0 (Adjuvants, Immunologic) RN - 0 (Antibodies, Fungal) RN - 0 (Antigens, Fungal) RN - 0 (CPG-oligonucleotide) RN - 0 (Cytokines) RN - 0 (Fungal Proteins) RN - 0 (Glycoproteins) RN - 0 (Oligodeoxyribonucleotides) SB - IM MH - Adjuvants, Immunologic/*pharmacology MH - Animals MH - Antibodies, Fungal/biosynthesis/blood MH - Antigens, Fungal/*genetics MH - Cell Proliferation MH - Cells, Cultured MH - Cytokines/metabolism MH - Dose-Response Relationship, Immunologic MH - Fungal Proteins/chemical synthesis/*genetics MH - Genes, Fungal/immunology MH - Glycoproteins/chemical synthesis/*genetics MH - Lymph Nodes/cytology/immunology/metabolism MH - Mice MH - Oligodeoxyribonucleotides/chemical synthesis/*pharmacology MH - Paracoccidioides/*genetics/growth & development/immunology MH - Paracoccidioidomycosis/immunology/pathology/*therapy MH - Spleen/microbiology/pathology MH - Th1 Cells/drug effects/*immunology MH - Th2 Cells/drug effects/*immunology EDAT- 2005/10/29 09:00 MHDA- 2005/12/13 09:00 CRDT- 2005/10/29 09:00 PHST- 2005/10/29 09:00 [pubmed] PHST- 2005/12/13 09:00 [medline] PHST- 2005/10/29 09:00 [entrez] AID - SJI1680 [pii] AID - 10.1111/j.1365-3083.2005.01680.x [doi] PST - ppublish SO - Scand J Immunol. 2005 Oct;62(4):325-33. doi: 10.1111/j.1365-3083.2005.01680.x.