title: Dextran sulfate sodium upregulates MAPK signaling for the uptake and subsequent intracellular survival of Brucella abortus in murine macrophages.
abstract: Brucellosis is one of the major zoonoses worldwide that inflicts important health problems in animal and human. Here, we demonstrated that dextran sulfate sodium (DSS) significantly increased adhesion of Brucella (B.) abortus in murine macrophages compared to untreated cells. Even without infection, Brucella uptake into macrophages increased and F-actin reorganization was induced compared with untreated cells. Furthermore, DSS increased the phosphorylation of MAPKs (ERK1/2 and p38α) in Brucella-infected, DSS-treated cells compared with the control cells. Lastly, DSS markedly increased the intracellular survival of Brucella abortus in macrophages by up to 48 h. These results suggest that DSS enhanced the adhesion and phagocytosis of B. abortus into murine macrophages by stimulating the MAPK signaling proteins phospho-ERK1/2 and p38α and that DSS increased the intracellular survival of B. abortus by inhibiting colocalization of Brucella-containing vacuoles (BCVs) with the late endosome marker LAMP-1. This study emphasizes the enhancement of the phagocytic and intracellular modulatory effects of DSS, which may suppress the innate immune system and contribute to prolonged Brucella survival and chronic infection.
authors.affiliation: Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, South Korea; Department of Veterinary Paraclinical Sciences, College of Veterinary Medicine, University of The Philippines Los Baños, College, Laguna 4031, Philippines.
authors.forename: Alisha Wehdnesday Bernardo
authors.initials: AW
authors.lastname: Reyes
authors.affiliation: Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, South Korea.
authors.forename: Lauren Togonon
authors.initials: LT
authors.lastname: Arayan
authors.affiliation: Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, South Korea.
authors.forename: Hannah Leah Tadeja
authors.initials: HL
authors.lastname: Simborio
authors.affiliation: Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, South Korea.
authors.forename: Huynh Tan
authors.initials: HT
authors.lastname: Hop
authors.affiliation: Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, South Korea.
authors.forename: WonGi
authors.initials: W
authors.lastname: Min
authors.affiliation: Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, South Korea.
authors.forename: Hu Jang
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: School of Medicine, Gyeongsang National University, Jinju, 660-701, South Korea.
authors.forename: Dong Hee
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Institute of Agriculture and Life Science, Gyeongsang National University, Jinju, 660-701, South Korea.
authors.forename: Hong Hee
authors.initials: HH
authors.lastname: Chang
authors.affiliation: Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, South Korea; Institute of Agriculture and Life Science, Gyeongsang National University, Jinju, 660-701, South Korea. Electronic address: hhchang@gnu.ac.kr.
authors.forename: Suk
authors.initials: S
authors.lastname: Kim
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion / Q000187:drug effects*; D002003:Brucella abortus / Q000187:drug effects* / Q000254:growth & development* / Q000502:physiology; D002006:Brucellosis / Q000235:genetics / Q000378:metabolism / Q000382:microbiology*; D016264:Dextran Sulfate / Q000494:pharmacology*; D054884:Host-Pathogen Interactions; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology*; D051379:Mice; D050296:Microbial Viability / Q000187:drug effects; D000067996:RAW 264.7 Cells; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016264:Dextran Sulfate
keywords: Adhesion; Brucella abortus; Dextran sulfate sodium; Internalization; Macrophage