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Poxvirus semaphorin A39R inhibits phagocytosis by dendritic cells and neutrophils

Thierry Walzer1, Laurent Galibert, Thibaut De Smedt

  • 1Amgen Inc., Seattle, WA 98119, USA. twalzer@yahoo.fr

European Journal of Immunology
|January 20, 2005
PubMed

Insights

Poxvirus A39R protein inhibits phagocytosis by immune cells like neutrophils and dendritic cells (DC) by binding to Plexin C1. This evasion mechanism impairs the immune system's ability to clear apoptotic cells and prime T cells.

Area of Science:

  • Immunology
  • Virology
  • Cell Biology

Background:

  • Poxvirus A39R protein, a semaphorin family member, binds Plexin C1 on neutrophils and dendritic cells (DC).
  • A39R binding to Plexin C1 disrupts actin cytoskeleton and inhibits integrin-mediated adhesion, causing cell retraction.
  • Phagocytosis relies on cytoskeleton integrity and integrin function.

Purpose of the Study:

  • To investigate the effect of A39R on DC and neutrophil phagocytosis.
  • To determine if A39R-mediated inhibition of phagocytosis is Plexin C1-dependent.
  • To assess the in vivo impact of A39R on antigen presentation and T cell priming.

Main Methods:

  • In vitro phagocytosis assays using DC and neutrophils treated with A39R.
  • In vivo studies assessing the uptake of apoptotic bodies by CD8alpha+ DC in A39R-treated mice.
  • Ex vivo and in vitro assays evaluating the capacity of DC to prime CD8+ T cells.

Main Results:

  • A39R treatment significantly inhibited phagocytosis by DC and neutrophils in a Plexin C1-dependent manner.
  • In vivo, A39R impaired the uptake of apoptotic bodies by CD8alpha+ DC.
  • A39R inhibited ex vivo cross-priming of CD8+ T cells by CD8alpha+ DC but did not affect direct priming in vitro.

Conclusions:

  • Poxvirus A39R protein inhibits phagocytosis and antigen presentation by immune cells.
  • Poxviruses may utilize semaphorin homologs like A39R to evade immune surveillance.
  • Targeting A39R-Plexin C1 interactions could be a strategy to enhance anti-viral immunity.

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