Salmonella Infection Blocks GC Development Via IL-12 Dependent Inhibition of T _FH Differentiation

Abstract

Germinal centers (GC) are crucial for the formation of long-lived humoral immunity. Many pathogens suppress GC, including Salmonella enterica serovar Typhimurium (STm), but the mechanisms driving suppression remain unknown. Using a mouse model of infection, we report that neither plasmablasts, nor even STm-specific B cells were required for GC suppression. Rather, we uncovered a failure in T_FH differentiation preceding GC suppression. We identified that IL-12, but not IFN-γ, suppressed T_FH differentiation T cell intrinsically. Administering recombinant IL-12 during NP-CGG immunization also suppressed T_FH differentiation and GC B cells, indicating that IL-12 is sufficient to suppress T_FH differentiation independent of STm infection. Therefore, IL-12 induced during STm infection in mice contributes to GC suppression via suppression of T_FH differentiation. More broadly, these data suggest that IL-12 can tailor the proportions of humoral (T_FH) and cellular (T_H1) immunity to the infection, with implications for IL-12 targeting therapies in autoimmunity and vaccination.

Keywords: Salmonella, TFH, Germinal Center, IL-12