Bacterial infection disrupts established germinal center reactions through monocyte recruitment and impaired metabolic adaptation [Bulk RNA-seq]

Consecutive exposures to different pathogens are very common and often alter host immune responses. Yet, it remains unknown how a secondary bacterial infection interferes with an ongoing adaptive immune response elicited against primary invading pathogens. Here, we demonstrate that pre-existing germinal center (GC) B cells are incapable of enduring radical metabolic changes induced by recruited Sca-1+ monocytes during Salmonella Typhimurium (STm) infection. GCs-induced by influenza, plasmodium and commensals deteriorated upon STm infection. GC collapse was independent of direct bacterial interactions with B cells, but rather, was induced through recruitment of CCR2-dependent Sca-1+ monocytes. GC collapse was dependent on non-B cell TLR-4, TNFa and IFN?, which was essential for Sca-1+ monocyte differentiation in the bone-marrow. Monocyte recruitment and GC disruption also occurred during LPS-supplemented vaccination and Listeria monocytogenes infection. Thus, systemic activation of the innate immune response upon lethal bacterial infection is induced at the expense of antibody-mediated immunity. Overall design: RNA-seq of GC B cells, monocytes and total tissue extract from Peyer's patches, 3 days after Salmonella infection