When carbon nanotubes encounter the immune system: desirable and undesirable effects.

The role of our immune system is to bring efficient protection against invasion by foreign elements, not only pathogens but also any material it may be in contact with. Nanoparticles may enter the body and encounter the immune system either intentionally (e.g. administration for biomedical application) or not (e.g. respiratory occupational exposure). Therefore, it is of fundamental importance to get a thorough knowledge of the way they interact with immune cells and all related consequences. Among nanomaterials, carbon nanotubes (CNTs) are of special interest because of their tremendous field of applications. Consequently, their increasing production, processing and eventual incorporation into new types of composites and/or into biological systems have raised fundamental issues regarding their potential impact on health. This review aims at giving an overview of the known desirable and undesirable effects of CNTs on the immune system, i.e. beneficial modulation of immune cells by CNTs engineered for biomedical applications versus toxicity, inflammation and unwanted immune reactions triggered by CNTs themselves.

[1]  A. Rao,et al.  A carbon nanotube toxicity paradigm driven by mast cells and the IL-₃₃/ST₂ axis. , 2012, Small.

[2]  Bengt Fadeel,et al.  Impaired Clearance and Enhanced Pulmonary Inflammatory/Fibrotic Response to Carbon Nanotubes in Myeloperoxidase-Deficient Mice , 2012, PloS one.

[3]  Craig A. Poland,et al.  Carbon nanotubes introduced into the abdominal cavity of mice show asbestos-like pathogenicity in a pilot study. , 2008, Nature nanotechnology.

[4]  Xu Wenli,et al.  Promises… , 1986 .

[5]  Carl A. Batt,et al.  Single-Walled Carbon Nanotubes Deliver Peptide Antigen into Dendritic Cells and Enhance IgG Responses to Tumor-Associated Antigens , 2011, ACS nano.

[6]  B. Erlanger,et al.  Antigenicity of fullerenes: antibodies specific for fullerenes and their characteristics. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[7]  P. Midgley,et al.  Toxicity and imaging of multi-walled carbon nanotubes in human macrophage cells. , 2009, Biomaterials.

[8]  Akihiko Hirose,et al.  Effects of sustained stimulation with multi-wall carbon nanotubes on immune and inflammatory responses in mice. , 2012, The Journal of toxicological sciences.

[9]  Craig A. Poland,et al.  The mechanism of pleural inflammation by long carbon nanotubes: interaction of long fibres with macrophages stimulates them to amplify pro-inflammatory responses in mesothelial cells , 2012, Particle and Fibre Toxicology.

[10]  V. Castranova,et al.  Identification of Systemic Markers from A Pulmonary Carbon Nanotube Exposure , 2011, Journal of occupational and environmental medicine.

[11]  H. Järventaus,et al.  Induction of chromosomal aberrations by carbon nanotubes and titanium dioxide nanoparticles in human lymphocytes in vitro , 2012, Nanotoxicology.

[12]  Martinus Løvik,et al.  Single-walled and multi-walled carbon nanotubes promote allergic immune responses in mice. , 2009, Toxicological sciences : an official journal of the Society of Toxicology.

[13]  Yuliang Zhao,et al.  Cytotoxicity of carbon nanomaterials: single-wall nanotube, multi-wall nanotube, and fullerene. , 2005, Environmental science & technology.

[14]  S. Bachilo,et al.  Near-infrared fluorescence microscopy of single-walled carbon nanotubes in phagocytic cells. , 2004, Journal of the American Chemical Society.

[15]  H. Dai,et al.  Complement activation by PEGylated single-walled carbon nanotubes is independent of C1q and alternative pathway turnover. , 2008, Molecular immunology.

[16]  Rajiv K. Saxena,et al.  Loss of Proliferation and Antigen Presentation Activity following Internalization of Polydispersed Carbon Nanotubes by Primary Lung Epithelial Cells , 2012, PloS one.

[17]  L. Pylkkänen,et al.  Engineered nanomaterials cause cytotoxicity and activation on mouse antigen presenting cells. , 2010, Toxicology.

[18]  Seishiro Hirano,et al.  Effects of multi-walled carbon nanotubes on a murine allergic airway inflammation model. , 2009, Toxicology and applied pharmacology.

[19]  Anwar Alam,et al.  Interactions of polydispersed single-walled carbon nanotubes with T cells resulting in downregulation of allogeneic CTL responses in vitro and in vivo , 2013, Nanotoxicology.

[20]  Judith Klein-Seetharaman,et al.  Adsorption of surfactant lipids by single-walled carbon nanotubes in mouse lung upon pharyngeal aspiration. , 2012, ACS nano.

[21]  Bengt Fadeel,et al.  Mechanisms of carbon nanotube-induced toxicity: focus on pulmonary inflammation. , 2013, Advanced drug delivery reviews.

[22]  Palaniappan Sethu,et al.  Evaluation of the Direct and Indirect Response of Blood Leukocytes to Carbon Nanotubes (cnts) , 2010 .

[23]  N. Wu,et al.  NLRP3 inflammasome activation in murine alveolar macrophages and related lung pathology is associated with MWCNT nickel contamination , 2012, Inhalation toxicology.

[24]  Yong Zhao,et al.  Peroxidase-mediated biodegradation of carbon nanotubes in vitro and in vivo. , 2013, Advanced drug delivery reviews.

[25]  Per Axel Clausen,et al.  Long, needle-like carbon nanotubes and asbestos activate the NLRP3 inflammasome through a similar mechanism. , 2011, ACS nano.

[26]  Judith Klein-Seetharaman,et al.  Biodegradation of single-walled carbon nanotubes by eosinophil peroxidase. , 2013, Small.

[27]  Chen Wang,et al.  Carbon Nanotubes Enhance Cytotoxicity Mediated by Human Lymphocytes In Vitro , 2011, PloS one.

[28]  A. Bianco,et al.  Oxidative biodegradation of single- and multi-walled carbon nanotubes. , 2011, Nanoscale.

[29]  Peng Wang,et al.  Multiwall carbon nanotubes mediate macrophage activation and promote pulmonary fibrosis through TGF-β/Smad signaling pathway. , 2013, Small.

[30]  S. Iijima Helical microtubules of graphitic carbon , 1991, Nature.

[31]  Chen Wang,et al.  Carbon nanotubes conjugated to tumor lysate protein enhance the efficacy of an antitumor immunotherapy. , 2008, Small.

[32]  Bengt Fadeel,et al.  Single-walled carbon nanotubes impair human macrophage engulfment of apoptotic cell corpses , 2009, Inhalation toxicology.

[33]  Liang-Hong Guo,et al.  Exposure of single-walled carbon nanotubes impairs the functions of primarily cultured murine peritoneal macrophages , 2013, Nanotoxicology.

[34]  Liang-Hong Guo,et al.  Single-walled carbon nanotubes and graphene oxides induce autophagosome accumulation and lysosome impairment in primarily cultured murine peritoneal macrophages. , 2013, Toxicology letters.

[35]  Tarek R. Fadel,et al.  Enhanced cellular activation with single walled carbon nanotube bundles presenting antibody stimuli. , 2008, Nano letters.

[36]  Eva Pebay-Peyroula,et al.  Proteins of the innate immune system crystallize on carbon nanotubes but are not activated. , 2011, ACS nano.

[37]  P. Midgley,et al.  Uptake of noncytotoxic acid-treated single-walled carbon nanotubes into the cytoplasm of human macrophage cells. , 2009, ACS nano.

[38]  J. Tschopp,et al.  Innate Immune Activation Through Nalp3 Inflammasome Sensing of Asbestos and Silica , 2008, Science.

[39]  Vitor Baranauskas,et al.  Up-regulation of T lymphocyte and antibody production by inflammatory cytokines released by macrophage exposure to multi-walled carbon nanotubes , 2011, Nanotechnology.

[40]  Scott W Burchiel,et al.  Pulmonary and systemic immune response to inhaled multiwalled carbon nanotubes. , 2007, Toxicological sciences : an official journal of the Society of Toxicology.

[41]  Y. Gun’ko,et al.  Recent Advances in Research on Carbon Nanotube–Polymer Composites , 2010, Advanced materials.

[42]  Maurizio Prato,et al.  Immunization with peptide-functionalized carbon nanotubes enhances virus-specific neutralizing antibody responses. , 2003, Chemistry & biology.

[43]  Alexander Star,et al.  Biodegradation of single-walled carbon nanotubes through enzymatic catalysis. , 2008, Nano letters.

[44]  A. Sokolov,et al.  PEGylated single-walled carbon nanotubes activate neutrophils to increase production of hypochlorous acid, the oxidant capable of degrading nanotubes. , 2012, Toxicology and applied pharmacology.

[45]  A. Casset,et al.  Immunomodulatory properties of multi-walled carbon nanotubes in peripheral blood mononuclear cells from healthy subjects and allergic patients. , 2013, Toxicology letters.

[46]  Roberto Madeddu,et al.  Ex vivo impact of functionalized carbon nanotubes on human immune cells. , 2012, Nanomedicine.

[47]  K. P. Murphy,et al.  Janeway's immunobiology , 2007 .

[48]  K. Rock,et al.  Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization , 2008, Nature Immunology.

[49]  Bengt Fadeel,et al.  Direct effects of carbon nanotubes on dendritic cells induce immune suppression upon pulmonary exposure. , 2011, ACS nano.

[50]  M. Prato,et al.  The alluring potential of functionalized carbon nanotubes in drug discovery , 2010, Expert opinion on drug discovery.

[51]  Robert B Sim,et al.  Complement activation by carbon nanotubes. , 2011, Advanced drug delivery reviews.

[52]  N. Bottini,et al.  Conjugation of antisense oligonucleotides to PEGylated carbon nanotubes enables efficient knockdown of PTPN22 in T lymphocytes. , 2009, Bioconjugate chemistry.

[53]  Hongjie Dai,et al.  siRNA delivery into human T cells and primary cells with carbon-nanotube transporters. , 2007, Angewandte Chemie.

[54]  Tarek R. Fadel,et al.  Adsorption of multimeric T cell antigens on carbon nanotubes: effect on protein structure and antigen-specific T cell stimulation. , 2013, Small.

[55]  N. Bottini,et al.  Multi-walled carbon nanotubes induce T lymphocyte apoptosis. , 2006, Toxicology letters.

[56]  P. Launois,et al.  Intracellular fate of carbon nanotubes inside murine macrophages: pH-dependent detachment of iron catalyst nanoparticles , 2013, Particle and Fibre Toxicology.

[57]  Peter Wick,et al.  A comparison of acute and long-term effects of industrial multiwalled carbon nanotubes on human lung and immune cells in vitro. , 2011, Toxicology letters.

[58]  Tatyana Chernova,et al.  Pulmonary toxicity of carbon nanotubes and asbestos - similarities and differences. , 2013, Advanced drug delivery reviews.

[59]  Feng Yang,et al.  Effect of multi-walled carbon nanotube surface modification on bioactivity in the C57BL/6 mouse model , 2014, Nanotoxicology.

[60]  D. Scheinberg,et al.  Carbon nanotubes as vaccine scaffolds. , 2013, Advanced drug delivery reviews.

[61]  Maurizio Prato,et al.  Immunological profile of a Plasmodium vivax AMA-1 N-terminus peptide-carbon nanotube conjugate in an infected Plasmodium berghei mouse model. , 2008, Vaccine.

[62]  Tarek R. Fadel,et al.  Clustering of stimuli on single-walled carbon nanotube bundles enhances cellular activation. , 2010, Langmuir : the ACS journal of surfaces and colloids.

[63]  K Kostarelos,et al.  Promises, facts and challenges for carbon nanotubes in imaging and therapeutics. , 2009, Nature nanotechnology.

[64]  Zongxi Li,et al.  Surface charge and cellular processing of covalently functionalized multiwall carbon nanotubes determine pulmonary toxicity. , 2013, ACS nano.

[65]  Kyunghee Choi,et al.  Pro-inflammatory and potential allergic responses resulting from B cell activation in mice treated with multi-walled carbon nanotubes by intratracheal instillation. , 2009, Toxicology.

[66]  Taro Shimizu,et al.  PEGylated liposomes elicit an anti-PEG IgM response in a T cell-independent manner. , 2007, Journal of controlled release : official journal of the Controlled Release Society.

[67]  Maurizio Prato,et al.  Cationic carbon nanotubes bind to CpG oligodeoxynucleotides and enhance their immunostimulatory properties. , 2005, Journal of the American Chemical Society.

[68]  Malcolm L. H. Green,et al.  Complement activation and protein adsorption by carbon nanotubes. , 2006, Molecular immunology.

[69]  P. Midgley,et al.  Direct imaging of single-walled carbon nanotubes in cells. , 2007, Nature nanotechnology.

[70]  M. Prato,et al.  Functionalized carbon nanotubes are non-cytotoxic and preserve the functionality of primary immune cells. , 2006, Nano letters.

[71]  Majid Zeinali,et al.  Immunological and cytotoxicological characterization of tuberculin purified protein derivative (PPD) conjugated to single-walled carbon nanotubes. , 2009, Immunology letters.

[72]  S W Burchiel,et al.  Mechanisms for how inhaled multiwalled carbon nanotubes suppress systemic immune function in mice. , 2009, Nature nanotechnology.

[73]  T. Andresen,et al.  Complement activation by PEG-functionalized multi-walled carbon nanotubes is independent of PEG molecular mass and surface density. , 2013, Nanomedicine : nanotechnology, biology, and medicine.

[74]  Judith Klein-Seetharaman,et al.  Carbon nanotubes degraded by neutrophil myeloperoxidase induce less pulmonary inflammation. , 2010, Nature nanotechnology.

[75]  Hongjie Dai,et al.  Single-walled carbon nanotube surface control of complement recognition and activation. , 2013, ACS nano.

[76]  E. Latz,et al.  Activation and regulation of the inflammasomes , 2013, Nature Reviews Immunology.