|
| Status |
Public on Sep 10, 2021 |
| Title |
MARCO+ lymphatic endothelial cells sequester arthritogenic alphaviruses in the draining lymph node and limit viral dissemination |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
While viremia in the vertebrate host is a critical determinant of arboviral reservoir competency, transmission efficiency, and disease severity, immune mechanisms that control arboviral viremia are poorly defined. Here, we identify critical roles for the scavenger receptor MARCO in controlling viremia during arthritogenic alphavirus infections in mice. Following subcutaneous inoculation, alphavirus particles drain via the lymph and are rapidly captured by MARCO+ lymphatic endothelial cells (LECs) in the draining lymph node (dLN), limiting viral spread to the bloodstream. Upon reaching the bloodstream, MARCO-expressing Kupffer cells in the liver remove circulating alphavirus particles, limiting viremia and further viral dissemination. MARCO-mediated accumulation of alphavirus particles in the lymph node and liver has important implications as viremia and viral tissue burdens are elevated in MARCO-/- mice and disease outcomes are more severe. These findings uncover a previously unrecognized pathogen scavenging role for LECs and improve our mechanistic understanding of viremia control during arboviral infections.
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| Overall design |
Identification of cells harboring CHIKV RNA using single-cell RNA sequencing.
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| Web link |
https://github.com/rnabioco/morrison-chikv
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| Contributor(s) |
Carpentier KS, Sheridan RM, Lucas CJ, Hesselberth JR, Morrison TE |
| Citation(s) |
34618370 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R01 AI141436 |
Impairment of B cell Responses by Pathogenic Chikungunya Viruses |
UNIVERSITY OF COLORADO DENVER |
THOMAS E MORRISON |
| R01 AI148144 |
Clearance of Blood-Borne Arboviruses |
UNIVERSITY OF COLORADO DENVER |
THOMAS E MORRISON |
| F32 AI140567 |
Viral and Host Determinants of Chikungunya Virus Dissemination |
UNIVERSITY OF COLORADO DENVER |
Kathryn Semmens Carpentier |
| F32 AI122463 |
Mechanisms of adaptive immune suppression during pathogenic chikungunya virus infection |
UNIVERSITY OF COLORADO DENVER |
Mary Katherine McCarthy |
| T32 AI007405 |
Training Program in Immunology |
UNIVERSITY OF COLORADO DENVER |
Ross M Kedl |
| T32 AI074491 |
Molecular Mechanisms of Immune Tolerance |
NATIONAL JEWISH HEALTH |
Roberta Pelanda |
| R35 GM119550 |
Biology of RNA damage and repair |
UNIVERSITY OF COLORADO DENVER |
Jay R Hesselberth |
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| |
| Submission date |
May 18, 2021 |
| Last update date |
Sep 23, 2023 |
| Contact name |
Jay R. Hesselberth |
| E-mail(s) |
jay.hesselberth@cuanschutz.edu
|
| Organization name |
University of Colorado School of Medicine
|
| Department |
Biochemistry and Molecular Gentetics
|
| Lab |
Jay Hesselberth
|
| Street address |
12801 E 17TH AVE
|
| City |
Aurora |
| State/province |
CO |
| ZIP/Postal code |
80045 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
|
| Samples (6)
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| Relations |
| BioProject |
PRJNA730926 |
| SRA |
SRP320410 |
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