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Impact of Silver and Carbon Nanoparticle Exposures on Macrophage Responses to Mycobacterium tuberculosis (M.tb)

Srijata Sarkar, Claudia Carranza, Ioannis Theodorou, Leo Bey Fen, Timothy Ellis, Alexandra Porter, Mary Ryan, Junfeng Zhang, Teresa Tetley and Stephan Schwander
J Immunol May 1, 2016, 196 (1 Supplement) 200.21;
Srijata Sarkar
1Rutgers Univ.
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Claudia Carranza
2Natl. Inst. of Resp. Dis., Mexico, Mexico
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Ioannis Theodorou
3Imperial Col. London, United Kingdom
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Leo Bey Fen
3Imperial Col. London, United Kingdom
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Timothy Ellis
3Imperial Col. London, United Kingdom
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Alexandra Porter
3Imperial Col. London, United Kingdom
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Mary Ryan
3Imperial Col. London, United Kingdom
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Junfeng Zhang
4Duke Univ.
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Teresa Tetley
3Imperial Col. London, United Kingdom
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Stephan Schwander
1Rutgers Univ.
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Abstract

To assess biological risks of nanoparticle (NP) exposures, we examined the effects of silver (Ag) core Ag20-citrate (Ag20) and carbon black (CB) on human host innate immune responses to M.tb, a respiratory pathogen that causes tuberculosis. Human peripheral blood monocyte-derived macrophages (MDMs) were exposed to 1, 10, 25 and 50 μg/mL of Ag20 and CB for 4 and 24 h. At 4 h no significant cytotoxicity was observed with neither of the NPs at none of the concentrations examined relative to unexposed MDMs. At 24 h, viability of the MDMs was reduced by 60–70% and 20% following Ag20 and CB exposure, respectively, at doses ≥25 μg/mL. M.tb-induced host immune responses are mediated by the activation of TLR signalling pathways that culminate in NF-κB activation. Effects of Ag20 and CB (10μg/mL for 4 h, a nontoxic dose) on TLR signalling in M.tb-infected and uninfected MDMs were compared using a human TLR signaling pathway-specific profiler array. Ag20 exposure suppressed the M.tb-induced expression of a subset of NF-κB-mediated target genes (CSF2, CSF3, IFNG, IL1A, IL1B, IL6, IL10, TNFA, NFKB1A). Ag20-mediated suppression of M.tb-induced activation of the TLR-signalling pathway was not due to decreased uptake of M.tb by MDMs or mycobacteriocidal effects of Ag20. Ag20 exposure increased the expression of HSPA1A mRNA that encodes for the stress-induced Hsp72. In contrast, exposure to CB resulted in little effects on M.tb-induced host gene expression indicating that immunosuppressive effects of Ag20 are NP-specific. Since Hsp72 has been shown to suppress NF-κB activation, we propose that Ag20-mediated Hsp72 upregulation contributes to the suppression of M.tb-induced NF-κB activation and host immune responses.

Funding NIEHS 5U19 ES019536

  • Copyright © 2016 by The American Association of Immunologists, Inc.
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The Journal of Immunology
Vol. 196, Issue 1 Supplement
1 May 2016
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Impact of Silver and Carbon Nanoparticle Exposures on Macrophage Responses to Mycobacterium tuberculosis (M.tb)
Srijata Sarkar, Claudia Carranza, Ioannis Theodorou, Leo Bey Fen, Timothy Ellis, Alexandra Porter, Mary Ryan, Junfeng Zhang, Teresa Tetley, Stephan Schwander
The Journal of Immunology May 1, 2016, 196 (1 Supplement) 200.21;

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Impact of Silver and Carbon Nanoparticle Exposures on Macrophage Responses to Mycobacterium tuberculosis (M.tb)
Srijata Sarkar, Claudia Carranza, Ioannis Theodorou, Leo Bey Fen, Timothy Ellis, Alexandra Porter, Mary Ryan, Junfeng Zhang, Teresa Tetley, Stephan Schwander
The Journal of Immunology May 1, 2016, 196 (1 Supplement) 200.21;
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Print ISSN 0022-1767        Online ISSN 1550-6606