The monoclonal antibody against the major diagnostic antigen of Paracoccidioides brasiliensis mediates immune protection in infected BALB/c mice challenged intratracheally with the fungus

被引:49
作者
Buissa-Filho, R. [1 ]
Puccia, R. [2 ]
Marques, A. F. [1 ]
Pinto, F. A. [1 ]
Munoz, J. E. [1 ]
Nosanchuk, J. D. [3 ,4 ]
Travassos, L. R. [2 ]
Taborda, C. P. [1 ]
机构
[1] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, BR-05508900 Sao Paulo, Brazil
[2] Univ Fed Sao Paulo, Dept Microbiol Immunol & Parasitol, Sao Carlos, SP, Brazil
[3] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA
[4] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA
关键词
D O I
10.1128/IAI.00349-08
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The protective role of specific antibodies against Paracoccidioides brasiliensis is controversial. In the present study, we analyzed the effects of monoclonal antibodies on the major diagnostic antigen (gp43) using in vitro and in vivo P. brasiliensis infection models. The passive administration of some monoclonal antibodies (MAbs) before and after intratracheal or intravenous infections led to a reduced fungal burden and decreased pulmonary inflammation. The protection mediated by MAb 3E, the most efficient MAb in the reduction of fungal burden, was associated with the enhanced phagocytosis of P. brasiliensis yeast cells by J774.16, MH-S, or primary macrophages. The ingestion of opsonized yeast cells led to an increase in NO production by macrophages. Passive immunization with MAb 3E induced enhanced levels of gamma interferon in the lungs of infected mice. The reactivity of MAb 3E against a panel of gp43-derived peptides suggested that the sequence NHVRIPIGWAV contains the binding epitope. The present work shows that some but not all MAbs against gp43 can reduce the fungal burden and identifies a new peptide candidate for vaccine development.
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收藏
页码:3321 / 3328
页数:8
相关论文
共 53 条
  • [1] Structure of the N-linked oligosaccharide of the main diagnostic antigen of the pathogenic fungus Paracoccidioides brasiliensis
    Almeida, IC
    Neville, DCA
    Mehlert, A
    Treumann, A
    Ferguson, MAJ
    Previato, JO
    Travassos, LR
    [J]. GLYCOBIOLOGY, 1996, 6 (05) : 507 - 515
  • [2] Melanin from Fonsecaea pedrosoi induces production of human antifungal antibodies and enhances the antimicrobial efficacy of phagocytes
    Alviano, DS
    Franzen, AJ
    Travassos, LR
    Holandino, C
    Rozental, S
    Ejzemberg, R
    Alviano, CS
    Rodrigues, ML
    [J]. INFECTION AND IMMUNITY, 2004, 72 (01) : 229 - 237
  • [3] [Anonymous], 1999, DEV COMP IMMUNOL
  • [4] [Anonymous], 1994, PARACOCCIDIOIDOMYCOS
  • [5] Both Th1 and Th2 cytokines affect the ability of monoclonal antibodies to protect mice against Cryptococcus neoformans
    Beenhouwer, DO
    Shapiro, S
    Feldmesser, M
    Casadevall, A
    Scharff, MD
    [J]. INFECTION AND IMMUNITY, 2001, 69 (10) : 6445 - 6455
  • [6] CAMARGO ZP, 1989, J MED VET MYCOL, V27, P407
  • [7] CAMARGO ZP, 1991, J MED VET MYCOL, V29, P31
  • [8] FATE OF CONIDIA OF PARACOCCIDIOIDES-BRASILIENSIS AFTER INGESTION BY RESIDENT MACROPHAGES OR CYTOKINE-TREATED MACROPHAGES
    CANO, LE
    BRUMMER, E
    STEVENS, DA
    RESTREPO, A
    [J]. INFECTION AND IMMUNITY, 1992, 60 (05) : 2096 - 2100
  • [9] INHIBITORY EFFECT OF DEFEROXAMINE OR MACROPHAGE ACTIVATION ON TRANSFORMATION OF PARACOCCIDIOIDES-BRASILIENSIS CONIDIA INGESTED BY MACROPHAGES - REVERSAL BY HOLOTRANSFERRIN
    CANO, LE
    GOMEZ, B
    BRUMMER, E
    RESTREPO, A
    STEVENS, DA
    [J]. INFECTION AND IMMUNITY, 1994, 62 (04) : 1494 - 1496
  • [10] Protective role of gamma interferon in experimental pulmonary paracoccidioidomycosis
    Cano, LE
    Kashino, SS
    Arruda, C
    André, D
    Xidieh, CF
    Singer-Vermes, LM
    Vaz, CAC
    Burger, E
    Calich, VLG
    [J]. INFECTION AND IMMUNITY, 1998, 66 (02) : 800 - 806