Critical role of zinc transporter (ZIP8) in myeloid innate immune cell function and the host response against bacterial pneumonia.

Details

• Personal Author:
  Bailey KL ; Dyavar SR ; Hall SC ; Knoell DL ; Samuelson DR ; Smith DR ; Wyatt TA
• Description:
  Zinc (Zn) is required for proper immune function and host defense. Zn homeostasis is tightly regulated by Zn transporters that coordinate biological processes through Zn mobilization. Zn deficiency is associated with increased susceptibility to bacterial infections, including Streptococcus pneumoniae, the most commonly identified cause of community-acquired pneumonia. Myeloid cells, including macrophages and dendritic cells (DCs), are at the front line of host defense against invading bacterial pathogens in the lung and play a critical role early on in shaping the immune response. Expression of the Zn transporter ZIP8 is rapidly induced following bacterial infection and regulates myeloid cell function in a Zn-dependent manner. To what extent ZIP8 is instrumental in myeloid cell function requires further study. Using a novel, myeloid-specific, Zip8 knockout model, we identified vital roles of ZIP8 in macrophage and DC function upon pneumococcal infection. Administration of S. pneumoniae into the lung resulted in increased inflammation, morbidity, and mortality in Zip8 knockout mice compared with wild-type counterparts. This was associated with increased numbers of myeloid cells, cytokine production, and cell death. In vitro analysis of macrophage and DC function revealed deficits in phagocytosis and increased cytokine production upon bacterial stimulation that was, in part, due to increased NF-kB signaling. Strikingly, alteration of myeloid cell function resulted in an imbalance of Th17/Th2 responses, which is potentially detrimental to host defense. These results (for the first time, to our knowledge) reveal a vital ZIP8- and Zn-mediated axis that alters the lung myeloid cell landscape and the host response against pneumococcus. [Description provided by NIOSH]
• Subjects:
  Blood Immune System Lung Macrophages Occupational Health Respiratory System Respiratory Tract Diseases Safety
• Keywords:
  Immune system; Immunology; Zinc; Bacterial infections; Pneumonia; Myeloid tissue; Macrophages; Cytokines; Lung cells
• ISSN:
  0022-1767
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Journal Article
• Place as Subject:
  Nebraska ; OSHA Region 7
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  207
• Issue:
  5
• NIOSHTIC Number:
  nn:20064793
• Citation:
  J Immunol 2021 Sep; 207(5):1357-1370
• Contact Point Address:
  Daren L. Knoell, University of Nebraska Medical Center, NE 68198-6120
• Email:
  daren.knoell@unmc.edu
• CAS Registry Number:
  Zinc (CAS RN 7440-66-6)
• Federal Fiscal Year:
  2021
• NORA Priority Area:
  Agriculture, Forestry and Fishing
• Performing Organization:
  University of Nebraska Medical Center - Omaha
• Peer Reviewed:
  True
• Start Date:
  20110901
• Source Full Name:
  The Journal of Immunology
• End Date:
  20270831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:078646a8a704f3481fb72483a25275d8f969bcdd91b56d0b95dc23dda4b5ae29df3f71000d9d5b736346b376d5ccc0e24964c5860ba2165ddb834c85333dc5ab
• Download URL:
  https://stacks.cdc.gov/view/cdc/248830/cdc_248830_DS1.pdf
• File Type:
  [PDF - 3.11 MB ]