title: Environmentally Relevant Level of Aflatoxin B1 Dysregulates Human Dendritic Cells Through Signaling on Key Toll-Like Receptors.
abstract: Aflatoxins (AFs) are highly hazardous fungal biometabolites usually present in feeds and foods. Aflatoxin B1(AFB1) is the most toxic and a known carcinogen. Toll-like receptors (TLRs), highly expressed by myeloid dendritic cells (DC), are key innate immune-surveillance molecules. Toll-like receptors not only sense pathogen-associated molecular patterns but also contribute to infections and cancer. To assess AFB1-TLR interactions on human myeloid DC, pure CD11c+DC were generated from monocytes isolated from healthy individuals and then exposed to relevant level of AFB1for 2 hours. Both quantitative polymerase chain reaction and flow cytometric assays were used to quantify, respectively, expression of TLR2 and TLR4 at the messenger RNA (mRNA) and protein levels in these DC. Levels of interleukin (IL) 1β, IL-6, and IL-10 were also analyzed in AFB1- and mock-treated DC. Compared to nontreated CD11c+DC, expression levels of both TLR2 and TLR4 mRNA and proteins were significantly upregulated in AFB1-treated cells. Further, although IL-10 levels in AFB1-treated DC were similar to those in the mock-treated DC, the AFB1-exposed DC secreted higher amounts of IL-1β and IL-6. Dendritic cells are sensitive to environmentally relevant level of AFB1, and TLR2 and TLR4 are involved in sensing AFB1Considering the broad roles of TLR2, TLR4, and DC in immunity and infections, our novel findings open a new door to understanding the molecular mechanisms and functional consequences of AFB1in inducing immunodysregulation, immunotoxicity, and thus (non)infectious diseases in humans.
authors.affiliation: Department of Pathobiology, Sections Immunology and Biotechnology, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran.|Veterinary Biotechnology Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran.
authors.forename: Azam
authors.initials: A
authors.lastname: Mohammadi
authors.affiliation: Department of Pathobiology, Sections Immunology and Biotechnology, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran mehrzad@um.ac.ir.|Veterinary Biotechnology Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran.
authors.forename: Jalil
authors.initials: J
authors.lastname: Mehrzad
authors.affiliation: Immunology Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Mahmoudi
authors.affiliation: Sektion Experimentelle Anästhesiologie, Universitätsklinikum Ulm, Ulm, Germany.
authors.forename: Marion
authors.initials: M
authors.lastname: Schneider
mesh_terms: D000328:Adult; D016604:Aflatoxin B1 / Q000633:toxicity*; D015415:Biomarkers / Q000378:metabolism; D039521:CD11c Antigen / Q000378:metabolism; D002274:Carcinogens, Environmental / Q000633:toxicity*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D016753:Interleukin-10 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D009994:Osmolar Concentration; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D051195:Toll-Like Receptor 2 / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D015415:Biomarkers; D039521:CD11c Antigen; D002274:Carcinogens, Environmental; C508609:IL10 protein, human; C508585:IL1B protein, human; C508600:IL6 protein, human; D053583:Interleukin-1beta; D015850:Interleukin-6; D012333:RNA, Messenger; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D016753:Interleukin-10; D016604:Aflatoxin B1
keywords: aflatoxin B1
              ; dendritic cells; immunotoxicity; qPCR; toll-like receptors