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, leading to B cell relocalization, loss of B cell-T cell borders, and lymphocyte depletion.
• Inflammatory myeloid cells infiltrate the lymph node during CHIKV infection, contributing to its disorganization.

Approach:

• Investigated CHIKV RNA accumulation in lymphatic endothelial cells (LECs) within the first 24 hours of infection.
• Analyzed the impact of CHIKV-MARCO interactions on inflammatory gene expression and myeloid cell recruitment.
• Assessed the changes in LEC numbers and function, specifically antigen acquisition, during CHIKV infection progression.

Key Points:

• CHIKV RNA accumulates in MARCO-expressing LECs in LN sinuses early in infection.
• Viral RNA accumulation triggers an antiviral and inflammatory gene expression program in LN stromal cells.
• CHIKV-MARCO interactions accelerate inflammatory responses and myeloid cell recruitment to the LN.
• Progression of CHIKV infection leads to a decrease in floor and medullary LECs, impairing LN function.
• Antigen acquisition by LECs is reduced during pathogenic CHIKV infection.

Conclusions:

• CHIKV infection directly impacts LECs, initiating an inflammatory cascade and compromising lymph node architecture and function.
• The interaction between CHIKV and MARCO-expressing LECs plays a critical role in modulating the early immune response within the lymph node.
• Impaired LEC function, including reduced antigen acquisition, contributes to the overall immune dysregulation observed during CHIKV infection.