Type I IFN stimulates lymph node stromal cells from adult and old mice during a West Nile virus infection

ABSTRACT: Advanced age is a significant risk factor during viral infection due to an age-associated decline in the immune response. While infection by West Nile virus (WNV) is typically mild, older individuals are at an increased risk of severe neuroinvasive disease. Previous studies have characterized age-associated defects in hematopoietic immune cells during WNV infection that culminate in diminished antiviral immunity. Situated amongst immune cells in the draining lymph node (DLN) are structural networks of nonhematopoietic lymph node stromal cells (LNSCs). LNSCs are comprised of numerous, diverse subsets, whose roles in the coordination of robust immune responses are underappreciated. Like lymphocytes, LNSCs mount tailored responses to viral pathogens and are susceptible to aging. However, the contributions of LNSCs to WNV immunity and immune senescence are unclear. Here, we examine LNSC responses to WNV infection within adult and old DLNs. Acute WNV infection was shown to trigger cellular infiltration and LNSC expansion. Comparatively, aged DLNs exhibited diminished leukocyte accumulation and altered LNSC subset composition. Upon recognition of WNV, adult and old LNSCs were activated in a distinct, type I interferon-driven mechanism that promoted antiviral gene expression. Aged LNSCs were found to constitutively upregulate immediate early response genes, several of which are associated with immune suppression. Collectively, these data suggest LNSCs uniquely respond to WNV infection via a novel activation mechanism. We are the first to report age-associated differences in LNSCs on the population- and gene expression-level during WNV infection. These changes may compromise antiviral immunity, leading to increased WNV disease in older individuals.

ORGANISM(S): Mus musculus

PROVIDER: GSE198629 | GEO | 2023/01/05

REPOSITORIES: GEO