Plasmodium berghei TatD-like DNase hijacks host innate immunity by inhibiting the TLR9-NF-κB pathway.

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  • Additional Information
    • Source:
      Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 100965259 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-1705 (Electronic) Linking ISSN: 15675769 NLM ISO Abbreviation: Int Immunopharmacol Subsets: MEDLINE
    • Publication Information:
      Original Publication: Amsterdam ; New York : Elsevier Science, c2001-
    • Subject Terms:
      Deoxyribonucleases*/metabolism ; Immunity, Innate* ; Macrophages*/immunology ; Macrophages*/metabolism ; Malaria*/immunology ; Malaria*/parasitology ; Neutrophils*/immunology ; Plasmodium berghei*/immunology ; Signal Transduction*; Animals ; Humans ; Mice ; Extracellular Traps/immunology ; Extracellular Traps/metabolism ; Mice, Inbred C57BL ; Mice, Knockout ; Myeloid Differentiation Factor 88/metabolism ; Myeloid Differentiation Factor 88/genetics ; NF-kappa B/metabolism ; Protozoan Proteins/metabolism ; Protozoan Proteins/immunology ; Protozoan Proteins/genetics ; Toll-Like Receptor 9/metabolism
    • Abstract:
      Neutrophils and macrophages confine pathogens by entrapping them in extracellular traps (ETs) through activating TLR9 function. However, plasmodial parasites secreted TatD-like DNases (TatD) to counteract ETs-mediated immune clearance. We found that TLR9 mutant mice increased susceptibility to rodent malaria, suggesting TLR9 is a key protein for host defense. We found that the proportion of neutrophils and macrophages in response to plasmodial parasite infection in the TLR9 mutant mice was significantly reduced compared to that of the WT mice. Importantly, PbTatD can directly bind to the surface TLR9 (sTLR9) on macrophages, which blocking the phosphorylation of mitogen-activated protein kinase and nuclear factor-κB, negatively regulated the signaling of ETs formation by both macrophages and neutrophils. Such, P. berghei TatD is a parasite virulence factor that can inhibit the proliferation of macrophages and neutrophils through directly binding to TLR9 receptors on the cell surface, thereby blocking the activation of the downstream MyD88-NF-kB pathways.
      Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
      (Copyright © 2024 Elsevier B.V. All rights reserved.)
    • Contributed Indexing:
      Keywords: Immune clearance; NETs; Plasmodium berghei; TLR9; TatD-like DNase
    • Accession Number:
      EC 3.1.- (Deoxyribonucleases)
      0 (Myeloid Differentiation Factor 88)
      0 (NF-kappa B)
      0 (Protozoan Proteins)
      0 (Tlr9 protein, mouse)
      0 (Toll-Like Receptor 9)
    • Publication Date:
      Date Created: 20240804 Date Completed: 20240831 Latest Revision: 20240909
    • Publication Date:
      20240909
    • Accession Number:
      10.1016/j.intimp.2024.112843
    • Accession Number:
      39098224