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
Abstract 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 syst...
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Veröffentlicht in: | Toxicological sciences 2020-08, Vol.176 (2), p.312-328 |
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description | Abstract
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. |
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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.</description><identifier>ISSN: 1096-6080</identifier><identifier>EISSN: 1096-0929</identifier><identifier>DOI: 10.1093/toxsci/kfaa080</identifier><identifier>PMID: 32514536</identifier><language>eng</language><publisher>OXFORD: Oxford University Press</publisher><subject>Developmental and Reproductive Toxicology ; Life Sciences & Biomedicine ; Science & Technology ; Toxicology</subject><ispartof>Toxicological sciences, 2020-08, Vol.176 (2), p.312-328</ispartof><rights>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 2020</rights><rights>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.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>14</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000593270200004</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c424t-362ebb6cb14eca30537d154682e56ecf469e95ed191fbb23878d99463262d0803</citedby><cites>FETCH-LOGICAL-c424t-362ebb6cb14eca30537d154682e56ecf469e95ed191fbb23878d99463262d0803</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,315,781,785,886,1585,27929,27930,28253</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32514536$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hsu, Kevin S</creatorcontrib><creatorcontrib>Goodale, Britton C</creatorcontrib><creatorcontrib>Ely, Kenneth H</creatorcontrib><creatorcontrib>Hampton, Thomas H</creatorcontrib><creatorcontrib>Stanton, Bruce A</creatorcontrib><creatorcontrib>Enelow, Richard I</creatorcontrib><title>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</title><title>Toxicological sciences</title><addtitle>TOXICOL SCI</addtitle><addtitle>Toxicol Sci</addtitle><description>Abstract
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.</description><subject>Developmental and Reproductive Toxicology</subject><subject>Life Sciences & Biomedicine</subject><subject>Science & Technology</subject><subject>Toxicology</subject><issn>1096-6080</issn><issn>1096-0929</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>AOWDO</sourceid><recordid>eNqNkU9v1DAQxSMEon_gyhH5imha20m88QUpWi1lpRWgUs6R40y2hsQOtrO0fCI-JrPKsoITXOzR-PeeR_OS5AWjl4zK7Cq6-6DN1ddOKVrSR8kpdkVKJZePD7XA_klyFsIXShkTVD5NTjJesLzIxGny85Ox2x5SDX1Pbt5XaYBvpLKqfwgmkBvYgeoDub1TkXz0YFVUPal8AGs0Wd2PLkweEAtTHwMxlmyc3aYR_HBBqnYHSJJV14HGV2fJehgmC-Qa8EC1hxAMtlGHFqOzSEdH1rbrJ7A_FKn2NYoRepY86XAUeH64z5PPb1e3y3fp5sP1elltUp3zPKaZ4NA0QjcsB60yWmSLlhW5KDkUAnSXCwmygJZJ1jUNz8pF2UqZi4wL3uKmsvPkzew7Ts0ArQYbverr0ZtB-YfaKVP__WLNXb11u3qRM3TZG1zOBtq7EDx0Ry2j9T6zes6sPmSGgpd__njEf4eEwOsZ-A6N61AKVsMRo5QWMuMLyrGiOdLl_9NLE9V-u0s32YjSV7PUTeO_pv4FaWDHYQ</recordid><startdate>20200801</startdate><enddate>20200801</enddate><creator>Hsu, Kevin S</creator><creator>Goodale, Britton C</creator><creator>Ely, Kenneth H</creator><creator>Hampton, Thomas H</creator><creator>Stanton, Bruce A</creator><creator>Enelow, Richard I</creator><general>Oxford University Press</general><general>Oxford Univ Press</general><scope>AOWDO</scope><scope>BLEPL</scope><scope>DTL</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>20200801</creationdate><title>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</title><author>Hsu, Kevin S ; Goodale, Britton C ; Ely, Kenneth H ; Hampton, Thomas H ; Stanton, Bruce A ; Enelow, Richard I</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c424t-362ebb6cb14eca30537d154682e56ecf469e95ed191fbb23878d99463262d0803</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Developmental and Reproductive Toxicology</topic><topic>Life Sciences & Biomedicine</topic><topic>Science & Technology</topic><topic>Toxicology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hsu, Kevin S</creatorcontrib><creatorcontrib>Goodale, Britton C</creatorcontrib><creatorcontrib>Ely, Kenneth H</creatorcontrib><creatorcontrib>Hampton, Thomas H</creatorcontrib><creatorcontrib>Stanton, Bruce A</creatorcontrib><creatorcontrib>Enelow, Richard I</creatorcontrib><collection>Web of Science - Science Citation Index Expanded - 2020</collection><collection>Web of Science Core Collection</collection><collection>Science Citation Index Expanded</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Toxicological sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hsu, Kevin S</au><au>Goodale, Britton C</au><au>Ely, Kenneth H</au><au>Hampton, Thomas H</au><au>Stanton, Bruce A</au><au>Enelow, Richard I</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>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</atitle><jtitle>Toxicological sciences</jtitle><stitle>TOXICOL SCI</stitle><addtitle>Toxicol Sci</addtitle><date>2020-08-01</date><risdate>2020</risdate><volume>176</volume><issue>2</issue><spage>312</spage><epage>328</epage><pages>312-328</pages><issn>1096-6080</issn><eissn>1096-0929</eissn><abstract>Abstract
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.</abstract><cop>OXFORD</cop><pub>Oxford University Press</pub><pmid>32514536</pmid><doi>10.1093/toxsci/kfaa080</doi><tpages>17</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Developmental and Reproductive Toxicology Life Sciences & Biomedicine Science & Technology Toxicology |
title | 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 |
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