Related Experiment Video
Updated: Jul 12, 2025
High-Throughput Transcriptome Analysis for Investigating Host-Pathogen Interactions
Published on: March 5, 2022
Chikungunya virus infection disrupts lymph node lymphatic endothelial cell composition and function via MARCO
Insights
Chikungunya virus (CHIKV) infection disrupts lymph node organization by targeting lymphatic endothelial cells (LECs). This impairs immune cell function and antigen acquisition, hindering the body's response to infection.
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.
Abstract:
Infection with chikungunya virus (CHIKV) causes disruption of draining lymph node (dLN) organization, including paracortical relocalization of B cells, loss of the B cell-T cell border, and lymphocyte depletion that is associated with infiltration of the LN with inflammatory myeloid cells. Here, we find that during the first 24 h of infection, CHIKV RNA accumulates in MARCO-expressing lymphatic endothelial cells (LECs) in both the floor and medullary LN sinuses. The accumulation of viral RNA in the LN was associated with a switch to an antiviral and inflammatory gene expression program across LN stromal cells, and this inflammatory response, including recruitment of myeloid cells to the LN, was accelerated by CHIKV-MARCO interactions. As CHIKV infection progressed, both floor and medullary LECs diminished in number, suggesting further functional impairment of the LN by infection. Consistent with this idea, we find that antigen acquisition by LECs, a key function of LN LECs during infection and immunization, was reduced during pathogenic CHIKV infection.
