PMID- 34918880 OWN - NLM STAT- MEDLINE DCOM- 20220929 LR - 20240102 IS - 1865-1682 (Electronic) IS - 1865-1674 (Linking) VI - 69 IP - 5 DP - 2022 Sep TI - Brucella induces heme oxygenase-1 expression to promote its infection. PG - 2697-2711 LID - 10.1111/tbed.14422 [doi] AB - Brucellosis is a zoonotic and contagious infectious disease caused by Brucella spp, which causes substantial economic losses to animal husbandry and leads to severe public health problems. Brucella have evolved multiple strategies to escape host immunity and survive within host cells. Elucidating the immune evasion strategies during Brucella infection will facilitate the control of brucellosis. The host enzyme, heme oxygenase-1 (HO-1), is a multifunctional protein that functions during inflammatory diseases and microbial infections. However, how HO-1 functions during Brucella infection is rarely studied. In this study, we evaluated the role of HO-1 during Brucella infection. We found that Brucella infection induced HO-1 expression in macrophages. We further showed that HO-1 was regulated by PI3K, AMPK kinase, and nuclear erythroid-related factor 2 (Nrf2) in macrophages. Interestingly, knocking out HO-1 or inhibiting the activity of HO-1 significantly decreased Brucella intracellular growth. Inducing the expression of HO-1 by treatment with CoPP promoted Brucella intracellular growth. Mechanistic analyses indicated that the effect of HO-1 was not meditated by HO-1 metabolites, but by decreasing the production of reactive oxygen species (ROS), TNF-alpha, and IL-1beta. Moreover, Brucella induced HO-1 expression in bone marrow-derived macrophages (BMDMs) and mice. When the expression of HO-1 was knocked down in BMDMs, the intracellular survival of Brucella was reduced. Furthermore, the induction of HO-1 by CoPP significantly increased bacterial loads in vivo. Thus, we demonstrated that Brucella induced HO-1 expression to promote its survival and growth in vitro and in vivo. This study also identified HO-1 as a novel innate immune evasion factor during Brucella infection. CI - (c) 2021 Wiley-VCH GmbH. FAU - Hu, Hai AU - Hu H AD - Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, P. R. China. FAU - Tian, Mingxing AU - Tian M AUID- ORCID: 0000-0002-6794-2639 AD - Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, P. R. China. FAU - Yin, Yi AU - Yin Y AD - Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, P. R. China. FAU - Zuo, Dong AU - Zuo D AD - Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, P. R. China. FAU - Guan, Xiang AU - Guan X AD - Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, P. R. China. FAU - Ding, Chan AU - Ding C AD - Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, P. R. China. AD - Jiangsu Coinnovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, P. R. China. FAU - Yu, Shengqing AU - Yu S AUID- ORCID: 0000-0003-1586-4277 AD - Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, P. R. China. AD - Jiangsu Coinnovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, P. R. China. LA - eng GR - 2021YFD1800402/National Key Research and Development Program of China/ GR - 31972723/National Natural Science Foundation of China/ GR - 32002318/National Natural Science Foundation of China/ GR - 32072828/National Natural Science Foundation of China/ PT - Journal Article DEP - 20220105 PL - Germany TA - Transbound Emerg Dis JT - Transboundary and emerging diseases JID - 101319538 RN - 0 (NF-E2-Related Factor 2) RN - 0 (Reactive Oxygen Species) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 1.14.14.18 (HMOX1 protein, human) RN - EC 1.14.14.18 (Heme Oxygenase-1) SB - IM MH - Animals MH - *Brucella MH - *Brucellosis/veterinary MH - Heme Oxygenase-1/genetics/metabolism MH - Mice MH - NF-E2-Related Factor 2/metabolism MH - Phosphatidylinositol 3-Kinases MH - Reactive Oxygen Species/metabolism MH - Tumor Necrosis Factor-alpha OTO - NOTNLM OT - Brucella OT - HO-1 OT - macrophages OT - reactive oxygen species EDAT- 2021/12/18 06:00 MHDA- 2022/09/30 06:00 CRDT- 2021/12/17 08:49 PHST- 2021/11/26 00:00 [revised] PHST- 2021/09/29 00:00 [received] PHST- 2021/12/08 00:00 [accepted] PHST- 2021/12/18 06:00 [pubmed] PHST- 2022/09/30 06:00 [medline] PHST- 2021/12/17 08:49 [entrez] AID - 10.1111/tbed.14422 [doi] PST - ppublish SO - Transbound Emerg Dis. 2022 Sep;69(5):2697-2711. doi: 10.1111/tbed.14422. Epub 2022 Jan 5.