Chikungunya virus impairs draining lymph node function by inhibiting HEV-mediated lymphocyte recruitment

Area of Science:

• Immunology
• Virology
• Pathology

Background:

• Chikungunya virus (CHIKV) causes significant acute and chronic rheumatologic conditions.
• Pathogenic CHIKV strains can persist in joints, while attenuated strains are cleared by adaptive immunity.
• The draining lymph node (dLN) is critical for initiating adaptive immune responses to CHIKV.

Purpose of the Study:

• To investigate the events within the draining lymph node (dLN) that lead to CHIKV persistence or clearance.
• To understand how pathogenic CHIKV strains disrupt lymphoid tissue organization and immune cell dynamics.

Main Methods:

• Comparative analysis of dLN structure and cellularity in mice infected with pathogenic versus attenuated CHIKV strains.
• Utilized CHIKV strains encoding ovalbumin-specific TCR epitopes to assess lymphocyte proliferation and trafficking.
• Investigated the role of high endothelial venules and CCL21 in lymphocyte homing.
• Assessed the impact of CHIKV infection on NP-specific germinal center B cells following NP-OVA immunization.

Main Results:

• Attenuated CHIKV (181/25) infection led to dLN enlargement and germinal center formation.
• Pathogenic CHIKV infection caused dLN disorganization and lymphocyte depletion.
• Lymphocyte depletion was linked to reduced naive lymphocyte accumulation, fewer high endothelial venule cells, and decreased CCL21.
• Pathogenic CHIKV infection reduced NP-specific germinal center B cells in the dLN.

Conclusions:

• Pathogenic CHIKV strains impair the development of adaptive immune responses within the dLN.
• The disruption of dLN architecture and lymphocyte trafficking by pathogenic CHIKV contributes to viral persistence.
• Understanding these mechanisms can inform strategies to control CHIKV infection and associated rheumatologic disease.