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

JCI Insight
Mary K McCarthyThomas E Morrison

Abstract

Chikungunya virus (CHIKV) causes acute and chronic rheumatologic disease. Pathogenic CHIKV strains persist in joints of immunocompetent mice, while the attenuated CHIKV strain 181/25 is cleared by adaptive immunity. We analyzed the draining lymph node (dLN) to define events in lymphoid tissue that may contribute to CHIKV persistence or clearance. Acute 181/25 infection resulted in dLN enlargement and germinal center (GC) formation, while the dLN of mice infected with pathogenic CHIKV became highly disorganized and depleted of lymphocytes. Using CHIKV strains encoding ovalbumin-specific TCR epitopes, we found that lymphocyte depletion was not due to impaired lymphocyte proliferation. Instead, the accumulation of naive lymphocytes transferred from the vasculature to the dLN was reduced, which was associated with fewer high endothelial venule cells and decreased CCL21 production. Following NP-OVA immunization, NP-specific GC B cells in the dLN were decreased during pathogenic, but not attenuated, CHIKV infection. Our data suggest that pathogenic, persistent strains of CHIKV disable the development of adaptive immune responses within the dLN.

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Citations

Dec 4, 2019·The Journal of Clinical Investigation·Anthony J LentscherTerence S Dermody
Sep 5, 2019·Nature Reviews. Rheumatology·Andreas Suhrbier
Jun 3, 2021·Cells·Abenaya Muralidharan, St Patrick Reid

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Datasets Mentioned

BETA
AF15561

Methods Mentioned

BETA
confocal microscopy
flow cytometry
FACS
ELISA

Software Mentioned

FACSDiva
ImmunoSpot
Tree Star
Elements AR
FlowJo
NIS
Imaris

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