Age-Dependent Cell Trafficking Defects in Draining Lymph Nodes Impair Adaptive Immunity and Control of West Nile Virus Infection

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While West Nile virus (WNV) infection preferentially causes severe neuroinvasive disease in elderly humans, the basis for this epidemiological linkage has remained uncertain. Here, we studied the impact of aging on WNV pathogenesis and immune responses using a mouse model of infection. Old mice showed increased lethality after WNV infection compared to adult mice, and this phenotype was associated with delayed antibody responses, and higher levels of virus infection in the blood, spleen, and brain. Detailed immunological and microscopic analyses revealed defects in germinal center development in the draining lymph node and impaired migratory capacity of naïve CD4+ T cells within days of WNV infection. This deficit was worsened by a separate age-related deficiency in the production of several chemokines that recruit leukocytes to inflamed lymph nodes. Thus, age-dependent defects in naïve CD4+ T cell trafficking and in the draining lymph node environment result in delayed initiation of antiviral responses and a failure to control WNV, which ultimately contributes to higher rates of mortality after infection.

Vyšlo v časopise: Age-Dependent Cell Trafficking Defects in Draining Lymph Nodes Impair Adaptive Immunity and Control of West Nile Virus Infection. PLoS Pathog 11(7): e32767. doi:10.1371/journal.ppat.1005027
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005027

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