4.7 Article

Strongylocentrotus nudus Eggs Polysaccharide Enhances Macrophage Phagocytosis Against E.coli Infection by TLR4/STAT3 Axis

Journal

FRONTIERS IN PHARMACOLOGY
Volume 13, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2022.807440

Keywords

SEP; macrophage; TLR4; phagocytosis; infection

Funding

  1. National Key Research and Development Program of China [2018YFA0902000]
  2. National Natural Science Foundation of China [82173863]
  3. Natural Science Foundation of Jiangsu Province of China [BK20201327]
  4. National Innovation and Entrepreneurship Training Program for Undergraduate [202110316047Z]
  5. Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
  6. Characteristic Subjects of Pharmacical Application in Hunan Province

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This study investigated whether Strongylocentrotus nudus eggs polysaccharide (SEP), a non-toxic extract from seafood, contributes to host defense against bacterial infection. The results showed that SEP enhanced bacterial clearance by promoting phagocytosis by macrophages and protected mice from bacterial infection.
Antibiotics resistance is one of the most significant public health threats globally. Strategies that strengthen host defenses to control pathogen infection has become a hot research field. Macrophages are part of early host defense mechanisms, and are activated via host pattern recognition receptors (PRRs), such as Toll-like receptor 4 (TLR4), which then facilitates phagocytosis and elimination of invading pathogens. However, few activators of PRRs have been approved for clinical use because of their toxic effects. This study aimed to investigate whether Strongylocentrotus nudus eggs polysaccharide (SEP), a non-toxic extract from seafood, contributes to host defense against bacterial infection. Results showed that SEP promoted bacterial clearance by enhancing phagocytosis by macrophages during E. coli infection in vitro, but was inhibited by TLR4 specific inhibitor TAK-242, STAT3 inhibitor Stattic or blockade of CD64. In addition, SEP protected mice from E. coli induced mortality, reduced pulmonary inflammation and inhibited dissemination of bacteria to organs, while TAK-242 retarded the protection of SEP. Overall, SEP strengthened innate host defense and improved the outcome in bacterial infection, suggesting that SEP could be used as a potential immunomodulator in host-directed therapies.

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