Environmental Immunology: Lessons Learned from Exposure to a Select Panel of Immunotoxicants

Kreitinger, J.; Beamer, Celine A.; Shepherd, David M.

doi:10.4049/jimmunol.1502149

Cited by 63 publications

(41 citation statements)

References 116 publications

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“…At present, human exposure to engineered NPs is widespread, through environmental routes (inhalation, ingestion, dermal contact and parenteral) or deliberate administration [6,7]. Interactions between nanoparticles(NPs) and the immune system have become important, and there are foundational questions about the safety of these special materials.…”

Section: Introductionmentioning

confidence: 99%

Effects of engineered nanoparticles on the innate immune system

Liu

Hardie

Zhang

et al. 2017

Seminars in Immunology

229

131

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Engineered nanoparticles (NPs) have broad applications in industry and nanomedicine. When NPs enter the body, interactions with the immune system are unavoidable. The innate immune system, a non-specific first line of defense against potential threats to the host, immediately interacts with introduced NPs and generates complicated immune responses. Depending on their physicochemical properties, NPs can interact with cells and proteins to stimulate or suppress the innate immune response, and similarly activate or avoid the complement system. NPs size, shape, hydrophobicity and surface modification are the main factors that influence the interactions between NPs and the innate immune system. In this review, we will focus on recent reports about the relationship between the physicochemical properties of NPs and their innate immune response, and their applications in immunotherapy.

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Section: Introductionmentioning

confidence: 99%

Effects of engineered nanoparticles on the innate immune system

Liu

Hardie

Zhang

et al. 2017

Seminars in Immunology

229

131

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“…AhR has been shown to be involved in mediating the biotransformation and carcinogenic/teratogenic effects of environmental toxins. Recently, its role in innate and adaptive immunity has been demonstrated, through its involvement in regulation of CD4, CD8 and Treg after viral infection [ 35 ]. We hypothesize that the outcome of dengue infection depends on a fine-tuning of the xenobiotic metabolism signaling pathway between the AhR and PP2A/CAR pathway.…”

Section: Discussionmentioning

confidence: 99%

Joint ancestry and association test indicate two distinct pathogenic pathways involved in classical dengue fever and dengue shock syndrome

et al. 2018

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Ethnic diversity has been long considered as one of the factors explaining why the severe forms of dengue are more prevalent in Southeast Asia than anywhere else. Here we take advantage of the admixed profile of Southeast Asians to perform coupled association-admixture analyses in Thai cohorts. For dengue shock syndrome (DSS), the significant haplotypes are located in genes coding for phospholipase C members (PLCB4 added to previously reported PLCE1), related to inflammation of blood vessels. For dengue fever (DF), we found evidence of significant association with CHST10, AHRR, PPP2R5E and GRIP1 genes, which participate in the xenobiotic metabolism signaling pathway. We conducted functional analyses for PPP2R5E, revealing by immunofluorescence imaging that the coded protein co-localizes with both DENV1 and DENV2 NS5 proteins. Interestingly, only DENV2-NS5 migrated to the nucleus, and a deletion of the predicted top-linking motif in NS5 abolished the nuclear transfer. These observations support the existence of differences between serotypes in their cellular dynamics, which may contribute to differential infection outcome risk. The contribution of the identified genes to the genetic risk render Southeast and Northeast Asian populations more susceptible to both phenotypes, while African populations are best protected against DSS and intermediately protected against DF, and Europeans the best protected against DF but the most susceptible against DSS.

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“…Hence, the dose of exposure, timing, route-of-administration, and target cell-type must all be scrutinized very carefully [ reviewed in (Safe et al , 2002; Kreitinger et al , 2016)].…”

Section: Ahr and Cell-signaling Pathwaysmentioning

confidence: 99%

Aryl hydrocarbon receptor (AHR): “pioneer member” of the basic-helix/loop/helix per - Arnt - sim (bHLH/PAS) family of “sensors” of foreign and endogenous signals

Nebert

2017

Progress in Lipid Research

220

191

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The basic-helix-loop-helix Per-Arnt-Sim (bHLH/PAS) family comprises many transcription factors, found throughout all three kingdoms of life; bHLH/PAS members “sense” innumerable intracellular and extracellular “signals” — including endogenous compounds, foreign chemicals, gas molecules, redox potential, photons (light), gravity, heat, and osmotic pressure. These signals then initiate downstream signaling pathways involved in responding to that signal. The term “PAS”, abbreviation for “Per-Arnt-Sim” was first coined in 1991. Although the mouse Arnt gene was not identified until 1991, evidence of its co-transcriptional binding partner, aryl hydrocarbon receptor (AHR), was first reported in 1974 as a “sensor” of foreign chemicals, up-regulating cytochrome P450 family 1 (CYP1) and other enzyme activities that usually metabolize the signaling chemical. Within a few years, AHR was proposed also to participate in inflammation. The mouse [Ah] locus was shown (1973–1989) to be relevant to chemical carcinogenesis, mutagenesis, toxicity and teratogenesis, the mouse Ahr gene was cloned in 1992, and the first Ahr(−/−) knockout mouse line was reported in 1995. After thousands of studies from the early 1970s to present day, we now realize that AHR participates in dozens of signaling pathways involved in critical-life processes, affecting virtually every organ and cell-type in the animal, including many invertebrates.

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Environmental Immunology: Lessons Learned from Exposure to a Select Panel of Immunotoxicants

Cited by 63 publications

References 116 publications

Effects of engineered nanoparticles on the innate immune system

Effects of engineered nanoparticles on the innate immune system

Joint ancestry and association test indicate two distinct pathogenic pathways involved in classical dengue fever and dengue shock syndrome

Aryl hydrocarbon receptor (AHR): “pioneer member” of the basic-helix/loop/helix per - Arnt - sim (bHLH/PAS) family of “sensors” of foreign and endogenous signals

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