Phospholipase A2 group IID is indispensable for coronavirus-specific humoral immune memory in middle aged mice Free

Phospholipases hydrolyze phospholipids to release long-chain fatty acids that are further metabolized sequentially by cyclooxygenases and synthases to yield various lipid mediators. Phospholipase A2 group IID (PLA₂G2D) is a member of phospholipases family and shows age-dependent increases in the lungs. In our previous study, we found that infection of mice lacking PLA₂G2D expression (Pla2g2d(−/−) mice) converted a lethal severe acute respiratory syndrome-coronavirus (SARS-CoV) infection to a nonlethal one (>80% survival), subsequent to enhanced respiratory dendritic cells (DCs) migration to the draining lymph nodes, augmented antivirus T cell responses, and diminished lung damage. However, the long-term effects of PLA₂G2D on host immune system against coronavirus remained unknow. In this study, we compared coronavirus-specific cellular and humoral immune memory induced by immunization or infection in middle-aged Pla2g2d^−/− mice and wild type mice. Surprisingly, virus-derived replicon (VRP)-immunized or sublethal dose-infected Pla2g2d^−/− mice failed to generate virus-specific neutralizing antibodies, which was accompanied by a lack of antibody-producing plasma cells and reduced follicular T cells (Tfh) compared to wild type mice. We hypothesize that PLA₂G2D deficiency in myeloid cells, likely DCs, play a critical role in the formation of CD4 T_fh cells and humoral immune memory against respiratory coronavirus infection.