"Obesity-induced systemic inflammation incurs severe viral infections and is associated with lower vaccination efficacy. Leveraging high-resolution omics and deep-learning-enabled function annotation tools, we conducted temporal tracking of immune networks in vaccinated mice challenged with Influenza to characterize obesity-skewed responses.
Temporal tracking confirmed the negative impact of obesity on vaccination, importantly, in a sex-dimorphic manner: obese females had significantly higher viral copies at the peak of infection with lower IFN-gamma and TNF-alpha in the lungs than obese males, and relative to their corresponding lean controls. Single-cell transcriptomics analysis of mediastinal lymph nodes revealed cell-to-cell communications critical for B cell activation (MHCII molecules, Cd86/Cd28, Cd40lg/Cd40, Il4r/Il4) were significantly repressed by obesity at baseline, post-vaccination, and during infection. Key pathways for B cell activation and T follicular helper interactions were also suppressed, dampening vaccination responses. Hence, we developed an omics-based, deep-learning-enabled tool, BRAY to annotate primary B cell functions. Application of BRAY detected suppressed cytokine production and antigen presentation in obesity; in line, obesity further inhibited plasma cells’ potential for antibody production.
Overall, our work revealed obesity-associated severe Influenza infections are underscored by deficient B cell activation and function. "