Macrophage sensing of single-walled carbon nanotubes via Toll-like receptors.
Sourav P MukherjeeOlesja BondarenkoPekka KohonenFernando T AndónTáňa BrzicováIsabel GessnerSanjay MathurMassimo BottiniPaolo CalligariLorenzo StellaElena KisinAnna ShvedovaReija AutioHeli Salminen-MankonenRiitta LahesmaaBengt FadeelPublished in: Scientific reports (2018)
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.
Keyphrases
- single cell
- dendritic cells
- genome wide
- toll like receptor
- carbon nanotubes
- walled carbon nanotubes
- immune response
- high throughput
- endothelial cells
- nuclear factor
- oxidative stress
- inflammatory response
- electronic health record
- induced apoptosis
- dna methylation
- big data
- signaling pathway
- cell cycle arrest
- lps induced
- adipose tissue
- regulatory t cells
- pi k akt
- bioinformatics analysis
- binding protein
- gram negative
- high resolution
- machine learning
- multidrug resistant
- ionic liquid
- artificial intelligence
- data analysis
- liver injury
- real time pcr
- liver fibrosis
- peripheral blood