Chikungunya virus infection disrupts lymph node lymphatic endothelial cell composition and function via MARCO

Area of Science:

• Immunology
• Virology
• Cell Biology

Background:

• Chikungunya virus (CHIKV) infection disrupts draining lymph node (dLN) organization.
• This disruption includes B cell relocalization, loss of B cell-T cell borders, and lymphocyte depletion.
• Inflammatory myeloid cells infiltrate the lymph node during CHIKV infection.

Purpose of the Study:

• To investigate the early interactions between CHIKV and lymphatic endothelial cells (LECs) within the lymph node.
• To understand how these interactions influence the lymph node's inflammatory response and overall function during infection.

Main Methods:

• Tracking CHIKV RNA accumulation in MARCO-expressing LECs in LN sinuses.
• Analyzing gene expression changes in LN stromal cells.
• Assessing the impact of CHIKV-MARCO interactions on inflammatory responses and myeloid cell recruitment.
• Quantifying LEC numbers and evaluating antigen acquisition by LECs during CHIKV infection.

Main Results:

• CHIKV RNA accumulated in MARCO-expressing LECs in floor and medullary LN sinuses within 24 hours.
• Viral RNA accumulation triggered antiviral and inflammatory gene programs in LN stromal cells.
• CHIKV-MARCO interactions accelerated inflammatory responses and myeloid cell recruitment.
• CHIKV infection led to a decrease in floor and medullary LECs and reduced their antigen acquisition function.

Conclusions:

• LECs are early targets of CHIKV infection in the lymph node.
• CHIKV-MARCO interactions drive lymph node inflammation and dysfunction.
• Impaired LEC function compromises crucial immune surveillance mechanisms during CHIKV infection.