| Institution: | 1. Department of Agricultural Biotechnology, College of Agriculture & Life Science, Seoul National University, Seoul 08826, Republic of Korea;2. Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 08826, Republic of Korea;1. School of Life Sciences, University of Warwick, Coventry, UK;2. Manchester Institute of Biotechnology & Photon Science Institute, The University of Manchester, Manchester, UK;3. Department of Chemistry, University of Warwick, Coventry, UK;1. Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan 250012, China;2. Blood Group Reference and Research Laboratory, Blood Center of Shandong Province, East Shanshi Road 22, Jinan, Shandong, China;3. Laboratory of Veterinary Hygiene, Graduate School of Veterinary Medicine and Life Science, Nippon Veterinary and Life Science University, Kyonan-cho 1-7-1, Musashino, Tokyo 180-8602, Japan;4. Department of Pathology, National Institute of Infectious Diseases, Gakuen 4-7-1, Musashi-murayama, Tokyo 208-0011, Japan;5. Division of Experimental Animals Research, National Institute of Infectious Diseases, Gakuen 4-7-1, Musashi-murayama, Tokyo 208-0011, Japan;6. Department of Virology II, National Institute of Infectious Diseases, Gakuen 4-7-1, Musashi-murayama, Tokyo 208-0011, Japan |
| Abstract: | Epoxide hydrolases (EHs) are enzymes that play roles in metabolizing xenobiotic epoxides from the environment, and in regulating lipid signaling molecules, such as juvenile hormones in insects and epoxy fatty acids in mammals. In this study we fed mosquitoes with an epoxide hydrolase inhibitor AUDA during artificial blood feeding, and we found the inhibitor increased the concentration of epoxy fatty acids in the midgut of female mosquitoes. We also observed ingestion of AUDA triggered early expression of defensin A, cecropin A and cecropin B2 at 6 h after blood feeding. The expression of cecropin B1 and gambicin were not changed more than two fold compared to controls. The changes in gene expression were transient possibly because more than 99% of the inhibitor was metabolized or excreted at 42 h after being ingested. The ingestion of AUDA also affected the growth of bacteria colonizing in the midgut, but did not affect mosquito longevity, fecundity and fertility in our laboratory conditions. When spiked into the blood, EpOMEs and DiHOMEs were as effective as the inhibitor AUDA in reducing the bacterial load in the midgut, while EETs rescued the effects of AUDA. Our data suggest that epoxy fatty acids from host blood are immune response regulators metabolized by epoxide hydrolases in the midgut of female mosquitoes, inhibition of which causes transient changes in immune responses, and affects growth of microbes in the midgut. |
