RT Journal Article
SR Electronic
T1 Impact of Silver and Carbon Nanoparticle Exposures on Macrophage Responses to <em>Mycobacterium tuberculosis</em> (<em>M.tb</em>)
JF The Journal of Immunology
JO J. Immunol.
FD American Association of Immunologists
SP 200.21
OP 200.21
VO 196
IS 1 Supplement
A1 Sarkar, Srijata
A1 Carranza, Claudia
A1 Theodorou, Ioannis
A1 Fen, Leo Bey
A1 Ellis, Timothy
A1 Porter, Alexandra
A1 Ryan, Mary
A1 Zhang, Junfeng
A1 Tetley, Teresa
A1 Schwander, Stephan
YR 2016
UL http://www.jimmunol.org/content/196/1_Supplement/200.21.abstract
AB 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