Age-specific dynamics of neutralizing antibodies, cytokines, and chemokines in response to La Crosse virus infection in mice

Abstract

AbstractLa Crosse virus (LACV) is a primary cause of pediatric arboviral encephalitis in the United States, with a notable impact on children aged 16 years or younger. This age-related susceptibility extends to murine models, where weanling mice (≤3 weeks old) succumb to LACV-induced disease, while adults (≥6 weeks old) demonstrate resistance. Despite its clinical significance, our understanding of host responses to LACV remains relatively unexplored. This study aims to elucidate the dynamics of neutralizing antibodies (nAbs), cytokines, and chemokines following LACV infection in both weanling and adult mice. Utilizing a highly infectious dose of LACV, our study reveals age-specific variations in viral titers, neutralizing antibody titers, and survivability. Weanling mice exhibit an early disease onset coupled with heightened peripheral viremia and nAbs compared to adults. Serum cytokine and chemokine profiling showed distinct kinetics and age-specific responses. Notably, adult mice exhibit significantly elevated levels of Th1 cytokines (IFN-γ, IL-18, GM-CSF, IL-1β and IL-12), juxtaposed with elevated levels of Th2 cytokines (IL-6 and IL-4) observed in weanling mice, often coinciding with the onset of symptoms. Furthermore, the heightened levels of Th9/Th17/Th22/Treg cytokines (IL-9, Il-10, IL-17A, IL-22, IL-23, and IL-27) and chemokines (CCL11, CCL3, and CCL5) in infected adult mice underscores their role in mounting protective immune responses against LACV. In conclusion, our study associates cytokines and chemokines with protective immunity in adult mice, contrasting with the pathogenesis observed in weanlings. This work emphasizes the need for further studies into mechanisms of innate and adaptive immune responses to LACV infection.