Cobalt (II) Chloride Regulates the Invasion and Survival of <i>Brucella abortus</i> 544 in RAW 264.7 Cells and B6 Mice

The effects of Cobalt (II) chloride (CoCl<sub>2</sub>) in the context of <i>Brucella abortus</i> (<i>B. abortus</i>) infection have not been evaluated so far. Firstly, we found that CoCl<sub>2</sub> treatment inhibited the phagocytosis of <i>B. a...

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Main Authors: Tran X. N. Huy, Trang T. Nguyen, Alisha W. B. Reyes, Heejin Kim, WonGi Min, Hu J. Lee, John H. Lee, Suk Kim
Format: Article
Language:English
Published: MDPI AG 2022-05-01
Series:Pathogens
Subjects:
Online Access:https://www.mdpi.com/2076-0817/11/5/596
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author Tran X. N. Huy
Trang T. Nguyen
Alisha W. B. Reyes
Heejin Kim
WonGi Min
Hu J. Lee
John H. Lee
Suk Kim
author_facet Tran X. N. Huy
Trang T. Nguyen
Alisha W. B. Reyes
Heejin Kim
WonGi Min
Hu J. Lee
John H. Lee
Suk Kim
author_sort Tran X. N. Huy
collection DOAJ
description The effects of Cobalt (II) chloride (CoCl<sub>2</sub>) in the context of <i>Brucella abortus</i> (<i>B. abortus</i>) infection have not been evaluated so far. Firstly, we found that CoCl<sub>2</sub> treatment inhibited the phagocytosis of <i>B. abortus</i> into RAW 264.7 cells. The inhibition of bacterial invasion was regulated by F-actin formation and associated with a reduction in the phosphorylation of ERK1/2 and HIF-1α expression. Secondly, the activation of trafficking regulators <i>LAMP1</i>, <i>LAMP2</i>, and lysosomal enzyme <i>GLA</i> at the transcriptional level activated immune responses, weakening the <i>B. abortus</i> growth at 4 h post-infection (pi). The silencing of HIF-1α increased bacterial survival at 24 h pi. At the same time, CoCl<sub>2</sub> treatment showed a significant increase in the transcripts of lysosomal enzyme <i>HEXB</i> and cytokine <i>TNF-α</i> and an attenuation of the bacterial survival. Moreover, the enhancement at the protein level of HIF-1α was induced in the CoCl<sub>2</sub> treatment at both 4 and 24 h pi. Finally, our results demonstrated that CoCl<sub>2</sub> administration induced the production of serum cytokines IFN-γ and IL-6, which is accompanied by dampened <i>Brucella</i> proliferation in the spleen and liver of treated mice, and reduced the splenomegaly and hepatomegaly. Altogether, CoCl<sub>2</sub> treatment contributed to host resistance against <i>B. abortus</i> infection with immunomodulatory effects.
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spelling doaj.art-f6fc86ae49c746149fb771df11a920622023-11-23T12:33:11ZengMDPI AGPathogens2076-08172022-05-0111559610.3390/pathogens11050596Cobalt (II) Chloride Regulates the Invasion and Survival of <i>Brucella abortus</i> 544 in RAW 264.7 Cells and B6 MiceTran X. N. Huy0Trang T. Nguyen1Alisha W. B. Reyes2Heejin Kim3WonGi Min4Hu J. Lee5John H. Lee6Suk Kim7Institute of Applied Sciences, HUTECH University, 475A Dien Bien Phu St., Ward 25, Binh Thanh District, Ho Chi Minh City 72300, VietnamInstitute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju 52828, KoreaDepartment of Veterinary Paraclinical Sciences, College of Veterinary Medicine, University of the Philippines Los Baños, College, Laguna 4031, PhilippinesInstitute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju 52828, KoreaInstitute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju 52828, KoreaInstitute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju 52828, KoreaCollege of Veterinary Medicine, Chonbuk National University, Iksan 54596, KoreaInstitute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju 52828, KoreaThe effects of Cobalt (II) chloride (CoCl<sub>2</sub>) in the context of <i>Brucella abortus</i> (<i>B. abortus</i>) infection have not been evaluated so far. Firstly, we found that CoCl<sub>2</sub> treatment inhibited the phagocytosis of <i>B. abortus</i> into RAW 264.7 cells. The inhibition of bacterial invasion was regulated by F-actin formation and associated with a reduction in the phosphorylation of ERK1/2 and HIF-1α expression. Secondly, the activation of trafficking regulators <i>LAMP1</i>, <i>LAMP2</i>, and lysosomal enzyme <i>GLA</i> at the transcriptional level activated immune responses, weakening the <i>B. abortus</i> growth at 4 h post-infection (pi). The silencing of HIF-1α increased bacterial survival at 24 h pi. At the same time, CoCl<sub>2</sub> treatment showed a significant increase in the transcripts of lysosomal enzyme <i>HEXB</i> and cytokine <i>TNF-α</i> and an attenuation of the bacterial survival. Moreover, the enhancement at the protein level of HIF-1α was induced in the CoCl<sub>2</sub> treatment at both 4 and 24 h pi. Finally, our results demonstrated that CoCl<sub>2</sub> administration induced the production of serum cytokines IFN-γ and IL-6, which is accompanied by dampened <i>Brucella</i> proliferation in the spleen and liver of treated mice, and reduced the splenomegaly and hepatomegaly. Altogether, CoCl<sub>2</sub> treatment contributed to host resistance against <i>B. abortus</i> infection with immunomodulatory effects.https://www.mdpi.com/2076-0817/11/5/596<i>Brucella abortus</i>CoCl<sub>2</sub>HIF-1αimmune responseRAW 264.7 cellB6 mouse
spellingShingle Tran X. N. Huy
Trang T. Nguyen
Alisha W. B. Reyes
Heejin Kim
WonGi Min
Hu J. Lee
John H. Lee
Suk Kim
Cobalt (II) Chloride Regulates the Invasion and Survival of <i>Brucella abortus</i> 544 in RAW 264.7 Cells and B6 Mice
Pathogens
<i>Brucella abortus</i>
CoCl<sub>2</sub>
HIF-1α
immune response
RAW 264.7 cell
B6 mouse
title Cobalt (II) Chloride Regulates the Invasion and Survival of <i>Brucella abortus</i> 544 in RAW 264.7 Cells and B6 Mice
title_full Cobalt (II) Chloride Regulates the Invasion and Survival of <i>Brucella abortus</i> 544 in RAW 264.7 Cells and B6 Mice
title_fullStr Cobalt (II) Chloride Regulates the Invasion and Survival of <i>Brucella abortus</i> 544 in RAW 264.7 Cells and B6 Mice
title_full_unstemmed Cobalt (II) Chloride Regulates the Invasion and Survival of <i>Brucella abortus</i> 544 in RAW 264.7 Cells and B6 Mice
title_short Cobalt (II) Chloride Regulates the Invasion and Survival of <i>Brucella abortus</i> 544 in RAW 264.7 Cells and B6 Mice
title_sort cobalt ii chloride regulates the invasion and survival of i brucella abortus i 544 in raw 264 7 cells and b6 mice
topic <i>Brucella abortus</i>
CoCl<sub>2</sub>
HIF-1α
immune response
RAW 264.7 cell
B6 mouse
url https://www.mdpi.com/2076-0817/11/5/596
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