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inhibits human innate immune responses via the production of TLR2 antagonist glycolipids. | LitMetric

AI Article Synopsis

  • The text discusses a study on a major human pathogen that can survive inside host cells and evade the immune system by inhibiting essential immune responses like phagosome maturation and cytokine production.* -
  • Researchers used a transposon mutant library of a virulent pathogen to identify mutants that activate NF-κB, a crucial immune regulator, revealing that one mutant lacked the ability to produce specific glycolipids known as sulfoglycolipids.* -
  • The study concludes that sulfoglycolipids act as antagonists for Toll-like receptors, specifically interfering with NF-κB activation and cytokine production, thereby showcasing a novel mechanism by which the pathogen undermines the innate immune defense and enhances its virulence.*

Article Abstract

is a major human pathogen that is able to survive inside host cells and resist immune clearance. Most particularly, it inhibits several arms of the innate immune response, including phagosome maturation or cytokine production. To better understand the molecular mechanisms by which circumvents host immune defenses, we used a transposon mutant library generated in a virulent clinical isolate of of the W/Beijing family to infect human macrophages, utilizing a cell line derivative of THP-1 cells expressing a reporter system for activation of the transcription factor NF-κB, a key regulator of innate immunity. We identified several mutants inducing a NF-κB activation stronger than that of the wild-type strain. One of these mutants was found to be deficient for the synthesis of cell envelope glycolipids, namely sulfoglycolipids, suggesting that the latter can interfere with innate immune responses. Using natural and synthetic molecular variants, we determined that sulfoglycolipids inhibit NF-κB activation and subsequent cytokine production or costimulatory molecule expression by acting as competitive antagonists of Toll-like receptor 2, thereby inhibiting the recognition of by this receptor. Our study reveals that producing glycolipid antagonists of pattern recognition receptors is a strategy used by to undermine innate immune defense. Sulfoglycolipids are major and specific lipids of , considered for decades as virulence factors of the bacilli. Our study uncovers a mechanism by which they may contribute to virulence.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5651758PMC
http://dx.doi.org/10.1073/pnas.1707840114DOI Listing

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