Human Innate Immune Cells Respond Differentially to Poly-γ-Glutamic Acid Polymers from Bacillus anthracis and Nonpathogenic Bacillus Species

Details

• Alternative Title:
  J Immunol
• Personal Author:
  Jelacic, Tanya M. ; Ribot, Wilson J. ; Chua, Jennifer ; Boyer, Anne E. ; Woolfitt, Adrian R. ; Barr, John R. ; Friedlander, Arthur M.
• Description:
  The poly-γ-glutamic acid (PGA) capsule produced by | is composed entirely of d-isomer glutamic acid, whereas nonpathogenic | species produce mixed d-, l-isomer PGAs. To determine if | PGA confers a pathogenic advantage over other PGAs, we compared the responses of human innate immune cells to | PGA and PGAs from nonpathogenic | subsp. | and | Monocytes and immature dendritic cells (iDCs) responded differentially to the PGAs, with | PGA being least stimulatory and | PGA most stimulatory. All three elicited IL-8 and IL-6 from monocytes, but | PGA also elicited IL-10 and TNF-α, whereas | PGA elicited all those plus IL-1β. Similarly, all three PGAs elicited IL-8 from iDCs, but | PGA also elicited IL-6, and | PGA elicited those plus IL-12p70, IL-10, IL-1β, and TNF-α. Only | PGA induced dendritic cell maturation. TLR assays also yielded differential results. | PGA and | PGA both elicited more TLR2 signal than | PGA, but only responses to | PGA were affected by a TLR6 neutralizing Ab. | PGA elicited more TLR4 signal than | PGA, whereas | PGA elicited none. | PGA persisted longer in high m.w. form in monocyte and iDC cultures than the other PGAs. Reducing the m.w. of | PGA reduced monocytes' cytokine responses. We conclude that | PGA is recognized less effectively by innate immune cells than PGAs from nonpathogenic | species, resulting in failure to induce a robust host response, which may contribute to anthrax pathogenesis.
• Subjects:
  Bacillus Anthracis Bacillus Licheniformis Bacillus Subtilis Cytokines Dendritic Cells Female Humans Immunity, Innate Macrophages Male Monocytes Polyglutamic Acid

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• Source:
  J Immunol. 204(5):1263-1273
• Pubmed ID:
  31932496
• Pubmed Central ID:
  PMC7970647
• Document Type:
  Journal Article
• Funding:
  CC999999/ImCDC/Intramural CDC HHSUnited States/
• Volume:
  204
• Issue:
  5
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:83e220a1ccb8aa3636328edc59158b6bac4613a41ce573d0ca0c84a92b6851376498cbd72860519e7225c9dd460d0bf7d01cf07af996b66ee6c7988c501eda94
• Download URL:
  https://stacks.cdc.gov/view/cdc/104326/cdc_104326_DS1.pdf
• File Type:
  [PDF - 1.47 MB ]