iBALT formation in the absence of lymphotoxin is protective in a lung β-coronavirus infection model 3230

Abstract Description The lymphotoxin signaling pathway mediates various immune responses, from lymph node organogenesis to dendritic cell homeostasis and differentiation of interferon-producing cells in response to pathogens. We investigated the lymphotoxin pathway during b-coronavirus lung infection with murine hepatitis virus strain 1 (MHV-1). Here, we report that while LTα1β2-LTβR is crucial for secondary lymphoid organ formation, the lung-associated tertiary lymphoid organ, iBALT (inducible Bronchus-Associated Lymphoid Tissue), is formed in mice deficient in Ltβ or Ltβr but not Tnfsf14, as determined by immunohistology and RNA-Seq analysis. During MHV-1 infection, the presence of LTβR-independent iBALT provided protection from increased viral load in the lung and overall morbidity. The results indicate that iBALT can form without an intact LTα1β2-LTβR signaling pathway and suggest an LTβR-independent, protective mechanism from β-coronavirus infection. Topic Categories Viral Immunology (VIR)