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https://www.arca.fiocruz.br/handle/icict/8521
OUTBREAK OF ACUTE CHAGAS DISEASE OCCURRED IN THE STATE OF BAHIA, BRAZIL
Linfócitos T CD8-Positivos/imunologia
Células Dendríticas/fisiologia
Produtos do Gene gag/fisiologia
HIV-1/fisiologia
Glicoproteínas de Membrana/biossíntese
Precursores de Proteínas/fisiologia
Virion/fisiologia
Técnicas de Cocultura
Humanos
Interferon gama/biossíntese
Interleucina-12/biossíntese
Ativação Linfocitária
Glicoproteínas de Membrana/fisiologia
Proteínas Citotóxicas Formadoras de Poros
Receptores de Superfície Celular/fisiologia
Saccharomyces cerevisiae/genética
Author
Affilliation
National Institute of Infectious Diseases. Department of Immunology. Shinjuku-ku.
Kitasato University. The Kitasato Institute for Life Sciences.
National Institute of Infectious Diseases. Department of Immunology. Shinjuku-ku.
University of Tokyo. Institute of Medical Science. Department of Infectious Diseases. Minato-ku, Tokyo, Japan.
University of Tokyo. Institute of Medical Science. Department of Infectious Diseases. Minato-ku, Tokyo, Japan.
University of Tokyo. Institute of Medical Science. Department of Infectious Diseases. Minato-ku, Tokyo, Japan.
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório Avançado de Saúde Pública. Salvador, BA, Brasil.
Hôpital Pitié-Salpêtrière. Laboratoire d’Immunologie Cellulaire et Tissulaire. Paris, France.
University of Tokyo. Institute of Medical Science. Department of Infectious Diseases. Minato-ku, Tokyo, Japan.
Kitasato University. The Kitasato Institute for Life Sciences.
National Institute of Infectious Diseases. Department of Immunology. Shinjuku-ku.
University of Tokyo. Institute of Medical Science. Department of Infectious Diseases. Minato-ku, Tokyo, Japan.
University of Tokyo. Institute of Medical Science. Department of Infectious Diseases. Minato-ku, Tokyo, Japan.
University of Tokyo. Institute of Medical Science. Department of Infectious Diseases. Minato-ku, Tokyo, Japan.
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório Avançado de Saúde Pública. Salvador, BA, Brasil.
Hôpital Pitié-Salpêtrière. Laboratoire d’Immunologie Cellulaire et Tissulaire. Paris, France.
University of Tokyo. Institute of Medical Science. Department of Infectious Diseases. Minato-ku, Tokyo, Japan.
Abstract
To evaluate the immunogenicity of human immunodeficiency virus (HIV) type 1 p55gag virus-like particles
(VLPs) released by budding from yeast spheroplasts, we have analyzed the effects of yeast VLPs on monocytederived
dendritic cells (DCs). Yeast VLPs were efficiently incorporated into DCs via both macropinocytosis and
endocytosis mediated by mannose-recognizing receptors, but not the mannose receptor. The uptake of yeast
VLPs induced DC maturation and enhanced cytokine production, notably, interleukin-12 p70. We showed that
yeast membrane components may contribute to DC maturation partly through Toll-like receptor 2 signaling.
Thus, Gag particles encapsulated by yeast membrane may have an advantage in stimulating Gag-specific
immune responses. We found that yeast VLPs, but not the control yeast membrane fraction, were able to
activate both CD4 and CD8 T cells of HIV-infected individuals. We tested the effect of cross-presentation of
VLP by DCs in two subjects recruited into a long-term nonprogressor-slow progressor cohort. When yeast
VLP-loaded DCs of these patients were cocultured with peripheral blood mononuclear cells for 7 days,
approximately one-third of the Gag-specific CD8 T cells were activated and became perforin positive.
However, some of the Gag-specific CD8 T cells appeared to be lost during in vitro culture, especially in a
patient with a high virus load. Our results suggest that DCs loaded with yeast VLPs can activate Gag-specific
memory CD8 T cells to become effector cells in chronically HIV-infected individuals, but there still remain
unresponsive Gag-specific T-cell populations in these patients.
DeCS
Apresentação do AntígenoLinfócitos T CD8-Positivos/imunologia
Células Dendríticas/fisiologia
Produtos do Gene gag/fisiologia
HIV-1/fisiologia
Glicoproteínas de Membrana/biossíntese
Precursores de Proteínas/fisiologia
Virion/fisiologia
Técnicas de Cocultura
Humanos
Interferon gama/biossíntese
Interleucina-12/biossíntese
Ativação Linfocitária
Glicoproteínas de Membrana/fisiologia
Proteínas Citotóxicas Formadoras de Poros
Receptores de Superfície Celular/fisiologia
Saccharomyces cerevisiae/genética
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