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PTX3 function as an opsonin for the dectin-1-dependent internalization of zymosan by macrophages

S N Diniz1, R Nomizo, P S Cisalpino

  • 1Ludwig Institute for Cancer Research, São Paulo, Brazil.

Journal of Leukocyte Biology
|January 17, 2004
PubMed

Insights

Pentraxin 3 (PTX3) enhances macrophage phagocytosis of fungi like Paracoccidioides brasiliensis. PTX3 acts as an opsonin, promoting innate immune response and fungal clearance via dectin-1.

Area of Science:

  • Immunology
  • Innate Immunity
  • Microbiology

Background:

  • Pentraxin 3 (PTX3) is a gene encoding a long pentraxin with known proinflammatory activity.
  • PTX3 expression is stimulated by tumor necrosis factor and interleukin-1beta.
  • The role of PTX3 in host defense against fungal pathogens remains to be fully elucidated.

Purpose of the Study:

  • To investigate the role of Pentraxin 3 (PTX3) in macrophage-mediated phagocytosis and microbicidal activity.
  • To determine the involvement of PTX3 in the recognition and clearance of fungal particles, specifically Paracoccidioides brasiliensis.
  • To explore the interaction between PTX3 and dectin-1 receptor in the innate immune response.

Main Methods:

  • Comparison of peritoneal macrophages from PTX3 transgenic (Tg) and wild-type (WT) mice.
  • Assessment of PTX3 mRNA levels, phagocytosis of zymosan (Zy) and P. brasiliensis yeast.
  • Flow cytometry and RT-PCR for Toll-like receptor-6 and dectin-1 expression; use of recombinant PTX3 protein and dectin-1 blockade.

Main Results:

  • Macrophages from PTX3 Tg mice exhibited higher basal and stimulated PTX3 mRNA levels compared to WT mice.
  • PTX3 Tg macrophages showed enhanced opsonin-independent phagocytosis and microbicidal activity against P. brasiliensis, with increased nitric oxide production.
  • Recombinant PTX3 protein demonstrated opsonin-like activity, promoting phagocytosis via dectin-1, which was crucial for zymosan uptake in both Tg and WT macrophages.

Conclusions:

  • Pentraxin 3 (PTX3) plays a significant role in the innate immune response by enhancing macrophage phagocytosis and microbicidal functions.
  • PTX3 acts as an opsonin, facilitating the recognition and clearance of fungal pathogens like P. brasiliensis.
  • The dectin-1 receptor is essential for PTX3-mediated phagocytosis, highlighting a key mechanism in host defense against fungal infections.

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