Single-cell RNA-seq Analysis Reveals That Prenatal Arsenic Exposure Results in Long-term, Adverse Effects on Immune Gene Expression in Response to Influenza A Infection.

Autor:	Hsu KS; Guarini School of Graduate and Advanced Studies at Dartmouth College, Hanover, New Hampshire 03755.; Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth College, Lebanon, New Hampshire 03766., Goodale BC; Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth College, Lebanon, New Hampshire 03766.; Dartmouth Toxic Metals Superfund Research Program, Hanover, New Hampshire 03755., Ely KH; Department of Medicine, Dartmouth-Hitchcock, Lebanon, New Hampshire 03766., Hampton TH; Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth College, Lebanon, New Hampshire 03766., Stanton BA; Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth College, Lebanon, New Hampshire 03766.; Dartmouth Toxic Metals Superfund Research Program, Hanover, New Hampshire 03755., Enelow RI; Guarini School of Graduate and Advanced Studies at Dartmouth College, Hanover, New Hampshire 03755.; Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth College, Lebanon, New Hampshire 03766.; Dartmouth Toxic Metals Superfund Research Program, Hanover, New Hampshire 03755.; Department of Medicine, Dartmouth-Hitchcock, Lebanon, New Hampshire 03766.
Jazyk:	angličtina
Zdroj:	Toxicological sciences : an official journal of the Society of Toxicology [Toxicol Sci] 2020 Aug 01; Vol. 176 (2), pp. 312-328.
DOI:	10.1093/toxsci/kfaa080
Abstrakt:	Arsenic exposure via drinking water is a serious environmental health concern. Epidemiological studies suggest a strong association between prenatal arsenic exposure and subsequent childhood respiratory infections, as well as morbidity from respiratory diseases in adulthood, long after systemic clearance of arsenic. We investigated the impact of exclusive prenatal arsenic exposure on the inflammatory immune response and respiratory health after an adult influenza A virus (IAV) lung infection. C57BL/6J mice were exposed to 100 ppb sodium arsenite in utero, and subsequently infected with IAV (H1N1) after maturation to adulthood. Assessment of lung tissue and bronchoalveolar lavage fluid at various time points post-IAV infection reveals greater lung damage and inflammation in arsenic-exposed mice versus control mice. Single-cell RNA sequencing analysis of immune cells harvested from IAV-infected lungs suggests that the enhanced inflammatory response is mediated by dysregulation of innate immune function of monocyte-derived macrophages, neutrophils, natural killer cells, and alveolar macrophages. Our results suggest that prenatal arsenic exposure results in lasting effects on the adult host innate immune response to IAV infection, long after exposure to arsenic, leading to greater immunopathology. This study provides the first direct evidence that exclusive prenatal exposure to arsenic in drinking water causes predisposition to a hyperinflammatory response to IAV infection in adult mice, which is associated with significant lung damage. (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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