Publications
2011
Al-Jamal Khuloud T, Nerl Hannah, Müller Karin H, Ali-Boucetta Hanene, Li Shouping, Haynes Peter D, Jinschek Joerg R, Prato Maurizio, Bianco Alberto, Kostarelos Kostas, Porter Alexandra E
Cellular uptake mechanisms of functionalised multi-walled carbon nanotubes by 3D electron tomography imaging Journal Article
In: Nanoscale, vol. 3, no. 6, pp. 2627–2635, 2011, ISSN: 2040-3372.
Abstract | Links | BibTeX | Tags: carbon, Cell Line, Cell Membrane, Cytoplasm, Electron Microscope Tomography, Humans, I2CT, imaging, Macrophages, Nanotubes, Phagocytosis, Phagosomes, Team-Bianco, Three-Dimensional, tumor
@article{al-jamal_cellular_2011,
title = {Cellular uptake mechanisms of functionalised multi-walled carbon nanotubes by 3D electron tomography imaging},
author = {Khuloud T Al-Jamal and Hannah Nerl and Karin H Müller and Hanene Ali-Boucetta and Shouping Li and Peter D Haynes and Joerg R Jinschek and Maurizio Prato and Alberto Bianco and Kostas Kostarelos and Alexandra E Porter},
doi = {10.1039/c1nr10080g},
issn = {2040-3372},
year = {2011},
date = {2011-06-01},
journal = {Nanoscale},
volume = {3},
number = {6},
pages = {2627--2635},
abstract = {Carbon nanotubes (CNTs) are being investigated for a variety of biomedical applications. Despite numerous studies, the pathways by which carbon nanotubes enter cells and their subsequent intracellular trafficking and distribution remain poorly determined. Here, we use 3-D electron tomography techniques that offer optimum enhancement of contrast between carbon nanotubes and the plasma membrane to investigate the mechanisms involved in the cellular uptake of shortened, functionalised multi-walled carbon nanotubes (MWNT-NH(3)(+)). Both human lung epithelial (A549) cells, that are almost incapable of phagocytosis and primary macrophages, capable of extremely efficient phagocytosis, were used. We observed that MWNT-NH(3)(+) were internalised in both phagocytic and non-phagocytic cells by any one of three mechanisms: (a) individually via membrane wrapping; (b) individually by direct membrane translocation; and (c) in clusters within vesicular compartments. At early time points following intracellular translocation, we noticed accumulation of nanotube material within various intracellular compartments, while a long-term (14-day) study using primary human macrophages revealed that MWNT-NH(3)(+) were able to escape vesicular (phagosome) entrapment by translocating directly into the cytoplasm.},
keywords = {carbon, Cell Line, Cell Membrane, Cytoplasm, Electron Microscope Tomography, Humans, I2CT, imaging, Macrophages, Nanotubes, Phagocytosis, Phagosomes, Team-Bianco, Three-Dimensional, tumor},
pubstate = {published},
tppubtype = {article}
}
Ogawa Michinaga, Yoshikawa Yuko, Kobayashi Taira, Mimuro Hitomi, Fukumatsu Makoto, Kiga Kotaro, Piao Zhenzi, Ashida Hiroshi, Yoshida Mitsutaka, Kakuta Shigeru, Koyama Tomohiro, Goto Yoshiyuki, Nagatake Takahiro, Nagai Shinya, Kiyono Hiroshi, Kawalec Magdalena, Reichhart Jean-Marc, Sasakawa Chihiro
A Tecpr1-dependent selective autophagy pathway targets bacterial pathogens Journal Article
In: Cell Host Microbe, vol. 9, no. 5, pp. 376–389, 2011, ISSN: 1934-6069.
Abstract | Links | BibTeX | Tags: Animals, Autophagy, Biological, Cells, Cultured, M3i, Membrane Proteins, Mice, Microtubule-Associated Proteins, Models, Phagosomes, Protein Interaction Mapping, reichhart, Shigella, Two-Hybrid System Techniques
@article{ogawa_tecpr1-dependent_2011,
title = {A Tecpr1-dependent selective autophagy pathway targets bacterial pathogens},
author = {Michinaga Ogawa and Yuko Yoshikawa and Taira Kobayashi and Hitomi Mimuro and Makoto Fukumatsu and Kotaro Kiga and Zhenzi Piao and Hiroshi Ashida and Mitsutaka Yoshida and Shigeru Kakuta and Tomohiro Koyama and Yoshiyuki Goto and Takahiro Nagatake and Shinya Nagai and Hiroshi Kiyono and Magdalena Kawalec and Jean-Marc Reichhart and Chihiro Sasakawa},
doi = {10.1016/j.chom.2011.04.010},
issn = {1934-6069},
year = {2011},
date = {2011-05-01},
journal = {Cell Host Microbe},
volume = {9},
number = {5},
pages = {376--389},
abstract = {Selective autophagy of bacterial pathogens represents a host innate immune mechanism. Selective autophagy has been characterized on the basis of distinct cargo receptors but the mechanisms by which different cargo receptors are targeted for autophagic degradation remain unclear. In this study we identified a highly conserved Tectonin domain-containing protein, Tecpr1, as an Atg5 binding partner that colocalized with Atg5 at Shigella-containing phagophores. Tecpr1 activity is necessary for efficient autophagic targeting of bacteria, but has no effect on rapamycin- or starvation-induced canonical autophagy. Tecpr1 interacts with WIPI-2, a yeast Atg18 homolog and PI(3)P-interacting protein required for phagophore formation, and they colocalize to phagophores. Although Tecpr1-deficient mice appear normal, Tecpr1-deficient MEFs were defective for selective autophagy and supported increased intracellular multiplication of Shigella. Further, depolarized mitochondria and misfolded protein aggregates accumulated in the Tecpr1-knockout MEFs. Thus, we identify a Tecpr1-dependent pathway as important in targeting bacterial pathogens for selective autophagy.},
keywords = {Animals, Autophagy, Biological, Cells, Cultured, M3i, Membrane Proteins, Mice, Microtubule-Associated Proteins, Models, Phagosomes, Protein Interaction Mapping, reichhart, Shigella, Two-Hybrid System Techniques},
pubstate = {published},
tppubtype = {article}
}
2008
Kwan Wing-Hong, Navarro-Sanchez Erika, Dumortier Hélène, Decossas Marion, Vachon Hortense, dos Santos Flavia Barreto, Fridman Hervé W, Rey Félix A, Harris Eva, Despres Philippe, Mueller Christopher G
Dermal-type macrophages expressing CD209/DC-SIGN show inherent resistance to dengue virus growth Journal Article
In: PLoS neglected tropical diseases, vol. 2, no. 10, pp. e311, 2008, ISSN: 1935-2735.
Abstract | Links | BibTeX | Tags: Adhesion, adhesion molecules, C-Type, Cell Adhesion, Cell Adhesion Molecules, Cell Line, Cell Surface, Cells, Chemistry, Cultured, Dendritic Cells, Dengue, Dengue virus, Gene Expression, Genetics, GLYCOPROTEIN, Growth, growth & development, Humans, ICAM-3, IFN ALPHA, IL-10, IL10, IMMATURE, Immunology, in situ, infection, LECTIN, Lectins, Macrophage, Macrophages, metabolism, METHOD, methods, monocyte, Monocytes, myeloid dendritic cells, pathogenesis, Phagosomes, PRODUCTION, Protein, Protein Binding, Proteins, Receptor, Receptors, Resistance, Skin, Team-Mueller, Viral Envelope Proteins, virology, virus
@article{kwan_dermal-type_2008b,
title = {Dermal-type macrophages expressing CD209/DC-SIGN show inherent resistance to dengue virus growth},
author = {Wing-Hong Kwan and Erika Navarro-Sanchez and Hélène Dumortier and Marion Decossas and Hortense Vachon and Flavia Barreto dos Santos and Hervé W Fridman and Félix A Rey and Eva Harris and Philippe Despres and Christopher G Mueller},
doi = {10.1371/journal.pntd.0000311},
issn = {1935-2735},
year = {2008},
date = {2008-10-01},
journal = {PLoS neglected tropical diseases},
volume = {2},
number = {10},
pages = {e311},
abstract = {BACKGROUND: An important question in dengue pathogenesis is the identity of immune cells involved in the control of dengue virus infection at the site of the mosquito bite. There is evidence that infection of immature myeloid dendritic cells plays a crucial role in dengue pathogenesis and that the interaction of the viral envelope E glycoprotein with CD209/DC-SIGN is a key element for their productive infection. Dermal macrophages express CD209, yet little is known about their role in dengue virus infection.
METHODS AND FINDINGS: Here, we showed that dermal macrophages bound recombinant envelope E glycoprotein fused to green fluorescent protein. Because dermal macrophages stain for IL-10 in situ, we generated dermal-type macrophages from monocytes in the presence of IL-10 to study their infection by dengue virus. The macrophages were able to internalize the virus, but progeny virus production was undetectable in the infected cells. In addition, no IFN-alpha was produced in response to the virus. The inability of dengue virus to grow in the macrophages was attributable to accumulation of internalized virus particles into poorly-acidified phagosomes.
CONCLUSIONS: Aborting infection by viral sequestration in early phagosomes would present a novel means to curb infection of enveloped virus and may constitute a prime defense system to prevent dengue virus spread shortly after the bite of the infected mosquito.},
keywords = {Adhesion, adhesion molecules, C-Type, Cell Adhesion, Cell Adhesion Molecules, Cell Line, Cell Surface, Cells, Chemistry, Cultured, Dendritic Cells, Dengue, Dengue virus, Gene Expression, Genetics, GLYCOPROTEIN, Growth, growth & development, Humans, ICAM-3, IFN ALPHA, IL-10, IL10, IMMATURE, Immunology, in situ, infection, LECTIN, Lectins, Macrophage, Macrophages, metabolism, METHOD, methods, monocyte, Monocytes, myeloid dendritic cells, pathogenesis, Phagosomes, PRODUCTION, Protein, Protein Binding, Proteins, Receptor, Receptors, Resistance, Skin, Team-Mueller, Viral Envelope Proteins, virology, virus},
pubstate = {published},
tppubtype = {article}
}
METHODS AND FINDINGS: Here, we showed that dermal macrophages bound recombinant envelope E glycoprotein fused to green fluorescent protein. Because dermal macrophages stain for IL-10 in situ, we generated dermal-type macrophages from monocytes in the presence of IL-10 to study their infection by dengue virus. The macrophages were able to internalize the virus, but progeny virus production was undetectable in the infected cells. In addition, no IFN-alpha was produced in response to the virus. The inability of dengue virus to grow in the macrophages was attributable to accumulation of internalized virus particles into poorly-acidified phagosomes.
CONCLUSIONS: Aborting infection by viral sequestration in early phagosomes would present a novel means to curb infection of enveloped virus and may constitute a prime defense system to prevent dengue virus spread shortly after the bite of the infected mosquito.