PMID- 11555401 OWN - NLM STAT- MEDLINE DCOM- 20011018 LR - 20190818 IS - 0300-9475 (Print) IS - 0300-9475 (Linking) VI - 54 IP - 4 DP - 2001 Oct TI - Immunostimulatory DNA from Paracoccidioides brasiliensis acts as T-helper 1 promoter in susceptible mice. PG - 348-56 AB - Th1 immune responses afford protection against some pathogens like the fungus P. brasiliensis (P.b.), etiological 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 P.b. 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 P.b. could have a immunostimulatory function as a Th-1-promoting adjuvant in susceptible mice. FAU - Souza, M C AU - Souza MC AD - Department of Microbiology, Immunology and Parasitology-Federal University of Sao Paulo (UNIFESP), Sao Paulo, SP, Brazil. FAU - Correa, M AU - Correa M FAU - Almeida, S R AU - Almeida SR FAU - Lopes, J D AU - Lopes JD FAU - Camargo, Z P AU - Camargo ZP 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 (DNA, Fungal) RN - 0 (Fungal Proteins) RN - 0 (Fungal Vaccines) RN - 0 (Glycoproteins) RN - 0 (Oligosaccharides) RN - 0 (Vaccines, DNA) RN - 207137-56-2 (Interleukin-4) RN - 31C4KY9ESH (Nitric Oxide) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - *Adjuvants, Immunologic MH - Animals MH - Antibodies, Fungal/blood MH - *Antigens, Fungal MH - Cells, Cultured MH - CpG Islands/*immunology MH - DNA Methylation MH - DNA, Fungal/*immunology MH - Disease Models, Animal MH - Disease Susceptibility MH - *Fungal Proteins MH - Fungal Vaccines/*immunology MH - Glycoproteins/*genetics MH - Interferon-gamma/biosynthesis/immunology/pharmacology MH - Interleukin-4/biosynthesis MH - Macrophages, Peritoneal/cytology/immunology/microbiology MH - Male MH - Mice MH - Nitric Oxide/biosynthesis MH - Oligosaccharides/*genetics MH - Paracoccidioides/genetics/growth & development/immunology MH - Paracoccidioidomycosis/*immunology/prevention & control MH - Phagocytosis/immunology MH - Th1 Cells/*immunology MH - Vaccines, DNA/*immunology EDAT- 2001/09/14 10:00 MHDA- 2001/10/19 10:01 CRDT- 2001/09/14 10:00 PHST- 2001/09/14 10:00 [pubmed] PHST- 2001/10/19 10:01 [medline] PHST- 2001/09/14 10:00 [entrez] AID - sji937 [pii] AID - 10.1046/j.1365-3083.2001.00937.x [doi] PST - ppublish SO - Scand J Immunol. 2001 Oct;54(4):348-56. doi: 10.1046/j.1365-3083.2001.00937.x.