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Human Innate Immune Cells Respond Differentially to Poly-γ-Glutamic Acid Polymers from Bacillus anthracis and Nonpathogenic Bacillus Species
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3 01 2020
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Source: J Immunol. 204(5):1263-1273
[PDF-1.47 MB]
Details:
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Alternative Title:J Immunol
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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.
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Pubmed ID:31932496
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Pubmed Central ID:PMC7970647
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