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Zinc transporter SLC39A7 relieves zinc deficiency to suppress alternative macrophage activation and impairment of phagocytosis

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  • Wenyan Xie
  • Qinghua Xue
  • Liangfei Niu
  • Ka-Wing Wong

Abstract

Macrophages are key phagocytic cells and play an important role in eliminating external microorganisms and endogenous danger signals. Dysregulation in macrophage functions have been reported in patients with asthma. Zinc homeostasis is critical in maintaining macrophage functions. The solute carrier (SLC) protein SLC39A7, a Zn2+ importer, has recently been linked to asthma. However, the roles of SLC39A7 in macrophage phagocytosis are not well understood. Here we found that phagocytosis efficiency was significantly decreased in SLC39A7-knockdown THP-1 cells, however the phagocytosis capability could be reversed with zinc supplementation. SLC39A7 deficiency skewed macrophages towards alternative activation, as indicated by increased expression of M2 activation marker CD206 and decreased expression of M1 activation marker NOS2. Consistent to this result, SLC39A7-knockdown cells produced reduced amounts of proinflammatory cytokines TNF- and IL-6. Furthermore, the mRNA level of receptor Clec4e previously known to be involved in phagocytosis of BCG was significantly reduced in SLC39A7 knockdown cells. Importantly, all these defects due to SLC39A7 deficiency could be reversed by zinc supplementation. Thus, zinc transporter SLC39A7 provide support for phagocytosis and classical macrophage activation.

Suggested Citation

  • Wenyan Xie & Qinghua Xue & Liangfei Niu & Ka-Wing Wong, 2020. "Zinc transporter SLC39A7 relieves zinc deficiency to suppress alternative macrophage activation and impairment of phagocytosis," PLOS ONE, Public Library of Science, vol. 15(7), pages 1-12, July.
    • Handle: RePEc:plo:pone00:0235776
    DOI: 10.1371/journal.pone.0235776
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    References listed on IDEAS

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    1. Ananda S. Prasad, 2020. "Zinc in Human Health," Chapters, in: Faik Atroshi (ed.), Personalized Medicine, in Relation to Redox State, Diet and Lifestyle, IntechOpen.
    2. Thomas A. Wynn & Ajay Chawla & Jeffrey W. Pollard, 2013. "Macrophage biology in development, homeostasis and disease," Nature, Nature, vol. 496(7446), pages 445-455, April.
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