Macrophage sensing of single- walled carbon nanotubes via Toll- like receptors

Authors

Sourav P. Mukherjee, Karolinska Institute
Olesja Bondarenko, Karolinska Institute & National Institute of Chemical Physics and Biophysics
Pekka Kohonen, Karolinska Institute
Fernando T. Andon, Karolinska Institute & Humanitas Clinical and Research Institute
Tana Brzicova, Karolinska Institute & Institute of Experimental Medicine AS CR
Isabel Gessner, University of Cologne
Sanjay Mathur, University of Cologne
Massimo Bottini, University of RomeTorVergata Rome & Sanford Burnham Prebys Medical Discovery Institute
Paolo Calligari, University of RomeTorVergata Rome
Lorenzo Stella, University of RomeTorVergata Rome
Elena Kisin, National Institute for Occupational Safety and Health
Anna Shvedova, National Institute for Occupational Safety and Health & West Virginia University
Reija Autio, University of Tampere
Heli Salminen-Mankonen, University of Turku
Ritta Lahesmaa, University of Turku
Bengt Fadeel, Karolinska Institute

Author ORCID Identifier

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https://orcid.org/0000-0002-7845-3611

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https://orcid.org/0000-0002-5489-7381

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Document Type

Article

Publication Date

2018

College/Unit

School of Medicine

Department/Program/Center

Medicine

Abstract

Carbon-based nanomaterials including carbon nanotubes (CNTs) have been shown to trigger

inflammation. However, how these materials are ‘sensed’ by immune cells is not known. Here we compared the effects of two carbon-based nanomaterials, single-walled CNTs (SWCNTs) and graphene oxide (GO), on primary human monocyte-derived macrophages. Genome-wide transcriptomics assessment was performed at sub-cytotoxic doses. Pathway analysis of the microarray data revealed pronounced effects on chemokine-encoding genes in macrophages exposed to SWCNTs, but not in response to GO, and these results were validated by multiplex array-based cytokine and chemokine profiling. Conditioned medium from SWCNT-exposed cells acted as a chemoattractant for dendritic cells. Chemokine secretion was reduced upon inhibition of NF-κB, as predicted by upstream regulator analysis of the transcriptomics data, and Toll-like receptors (TLRs) and their adaptor molecule, MyD88 were shown to be important for CCL5 secretion. Moreover, a specific role for TLR2/4 was confirmed by using reporter cell lines. Computational studies to elucidate how SWCNTs may interact with TLR4 in the absence of a protein corona suggested that binding is guided mainly by hydrophobic interactions. Taken together, these results imply that CNTs may be ‘sensed’ as pathogens by immune cells.

Digital Commons Citation

Mukherjee, Sourav P.; Bondarenko, Olesja; Kohonen, Pekka; Andon, Fernando T.; Brzicova, Tana; Gessner, Isabel; Mathur, Sanjay; Bottini, Massimo; Calligari, Paolo; Stella, Lorenzo; Kisin, Elena; Shvedova, Anna; Autio, Reija; Salminen-Mankonen, Heli; Lahesmaa, Ritta; and Fadeel, Bengt, "Macrophage sensing of single- walled carbon nanotubes via Toll- like receptors" (2018). Faculty & Staff Scholarship. 1852.
https://researchrepository.wvu.edu/faculty_publications/1852

Source Citation

Mukherjee, S. P., Bondarenko, O., Kohonen, P., Andón, F. T., Brzicová, T., Gessner, I., Mathur, S., Bottini, M., Calligari, P., Stella, L., Kisin, E., Shvedova, A., Autio, R., Salminen-Mankonen, H., Lahesmaa, R., & Fadeel, B. (2018). Macrophage sensing of single-walled carbon nanotubes via Toll-like receptors. Scientific Reports, 8(1). https://doi.org/10.1038/s41598-018-19521-9

Comments

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