NDV entry into dendritic cells through macropinocytosis and suppression of T lymphocyte proliferation

Area of Science:

• Virology
• Immunology
• Cell Biology

Background:

• Newcastle disease virus (NDV) poses significant economic threats to the poultry sector.
• NDV employs diverse cellular pathways for infection, including interactions with dendritic cells (DCs).

Purpose of the Study:

• To elucidate the mechanisms of NDV entry into DCs.
• To investigate the immunomodulatory effects of NDV on DCs and T cells.
• To explore NDV's role in DC apoptosis and T cell proliferation inhibition.

Main Methods:

• Investigated NDV entry pathways into DCs, focusing on macropinocytosis and clathrin-mediated endocytosis.
• Quantified cytokine production (IFN-γ, TNF-α, IL-12, IL-4, IL-10) in response to NDV.
• Assessed the expression of TRAIL and cleaved caspase-3 to evaluate apoptosis.
• Utilized Transwell® co-culture to study the impact of NDV-stimulated DCs on T cell proliferation.

Main Results:

• NDV primarily enters DCs via macropinocytosis and clathrin-mediated endocytosis.
• NDV infection significantly boosted Th1 cytokine production (IFN-γ, TNF-α, IL-12) while suppressing Th2 responses (IL-4, IL-10).
• NDV induced DC apoptosis through the extrinsic pathway, evidenced by increased TRAIL and cleaved caspase-3.
• Direct contact with live NDV-stimulated DCs, but not inactivated NDV, inhibited CD4+ T cell proliferation.

Conclusions:

• NDV utilizes specific endocytic pathways to infect DCs, modulating immune responses.
• NDV induces DC apoptosis and suppresses T cell proliferation, impacting adaptive immunity.
• These findings offer critical insights into NDV pathogenesis and immune evasion strategies.