Journal article
Age-Dependent Cell Trafficking Defects in Draining Lymph Nodes Impair Adaptive Immunity and Control of West Nile Virus Infection
PLoS pathogens, v 11(7), pp e1005027-e1005027
01 Jul 2015
PMID: 26204259
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Impaired immune responses in the elderly lead to reduced vaccine efficacy and increased susceptibility to viral infections. Although several groups have documented age-dependent defects in adaptive immune priming, the deficits that occur prior to antigen encounter remain largely unexplored. Herein, we identify novel mechanisms for compromised adaptive immunity that occurs with aging in the context of infection with West Nile virus (WNV), an encephalitic flavivirus that preferentially causes disease in the elderly. An impaired IgM and IgG response and enhanced vulnerability to WNV infection during aging was linked to delayed germinal center formation in the draining lymph node (DLN). Adoptive transfer studies and two-photon intravital microscopy revealed a decreased trafficking capacity of donor naive CD4(+) T cells from old mice, which manifested as impaired T cell diapedesis at high endothelial venules and reduced cell motility within DLN prior to antigen encounter. Furthermore, leukocyte accumulation in the DLN within the first few days of WNV infection or antigen-adjuvant administration was diminished more generally in old mice and associated with a second aging-related defect in local cytokine and chemokine production. Thus, age-dependent cell-intrinsic and environmental defects in the DLN result in delayed immune cell recruitment and antigen recognition. These deficits compromise priming of early adaptive immune responses and likely contribute to the susceptibility of old animals to acute WNV infection.
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Details
- Title
- Age-Dependent Cell Trafficking Defects in Draining Lymph Nodes Impair Adaptive Immunity and Control of West Nile Virus Infection
- Creators
- Justin M. Richner - Washington University in St. LouisGrzegorz B. Gmyrek - Washington University in St. LouisJennifer Govero - Washington University in St. LouisYizheng Tu - Washington University in St. LouisGerritje J. W. van der Windt - Washington University in St. LouisTalibah U. Metcalf - Vaccine & Gene Therapy Institute of FloridaElias K. Haddad - Vaccine & Gene Therapy Institute of FloridaJohannes Textor - Utrecht UniversityMark J. Miller - College Station Medical CenterMichael S. Diamond - College Station Medical Center
- Publication Details
- PLoS pathogens, v 11(7), pp e1005027-e1005027
- Publisher
- Public Library Science
- Number of pages
- 29
- Grant note
- HHSN272201100017C; R01-AI091965; R01-AI07760; F32-AG043223 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01AI091965 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) F32AG043223 / NATIONAL INSTITUTE ON AGING; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA) 823.02.014 / Netherlands Organisation for Scientific Research (NWO); Netherlands Organization for Scientific Research (NWO)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- College of Medicine; Physician Assistant; Infectious Diseases (and HIV Medicine); Drexel University
- Web of Science ID
- WOS:000359365200041
- Scopus ID
- 2-s2.0-84938777751
- Other Identifier
- 991020100053304721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Microbiology
- Parasitology
- Virology