Lipocalin 2 (Lcn2) interferes with iron uptake by Brucella abortus and dampens immunoregulation during infection of RAW 264.7 macrophages |
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| Authors: | Huynh Tan Hop Lauren Togonon Arayan Tran Xuan Ngoc Huy Alisha Wehdnesday Bernardo Reyes Eun Jin Baek Wongi Min Hu Jang Lee Man Hee Rhee Kenta Watanabe Hong Hee Chang Suk Kim |
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| Affiliation: | 1. Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju, Republic of Korea;2. College of Veterinary Medicine, Kyungpook National University, Daegu, Republic of Korea;3. The United Graduate School of Veterinary Science, Yamaguchi University, Yamaguchi, Japan;4. Institute of Agriculture and Life Science, Gyeongsang National University, Jinju, Republic of Korea |
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| Abstract: | Lipocalin 2 (Lcn2) is an important innate immunity component against bacterial pathogens. In this study, we report that Lcn2 is induced by Brucella (B.) abortus infection and significantly contributes to the restriction of intracellular survival of Brucella in macrophages. We found that Lcn2 prevented iron uptake by B. abortus through two distinct mechanisms. First, Lcn2 is secreted to capture bacterial siderophore(s) and abrogate iron import by Brucella. Second, Lcn2 decreases the intracellular iron levels during Brucella infection, which probably deprives the invading Brucella of the iron source needed for growth. Suppression of Lcn2 signalling resulted in a marked induction of anti‐inflammatory cytokine, interleukin 10, which was shown to play a major role in Lcn2‐induced antibrucella immunity. Similarly, interleukin 6 was also found to be increased when Lcn2 signalling is abrogated; however, this induction was thought to be an alternative pathway that rescues the cell from infection when the effective Lnc2 pathway is repressed. Furthermore, Lcn2 deficiency also caused a marked decrease in brucellacidal effectors, such as reactive oxygen species and nitric oxide but not the phagolysosome fusion. Taken together, our results indicate that Lcn2 is required for the efficient restriction of intracellular B. abortus growth that is through limiting iron acquisition and shifting cells to pro‐inflammatory brucellacidal activity in murine macrophages. |
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| Keywords: | apoptosis Brucella abortus iron sequestrating lipocalin 2 NO ROS |
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