Consecutive exposures to different pathogens are highly prevalent and often alter the host immune response. However, it remains unknown how a secondary bacterial infection affects an ongoing adaptive immune response elicited against primary invading pathogens. We demonstrated that recruitment of Sca-1 monocytes into lymphoid organs during Salmonella Typhimurium (STm) infection disrupted pre-existing germinal center (GC) reactions. GC responses induced by influenza, plasmodium, or commensals deteriorated following STm infection. GC disruption was independent of the direct bacterial interactions with B cells and instead was induced through recruitment of CCR2-dependent Sca-1 monocytes into the lymphoid organs. GC collapse was associated with impaired cellular respiration and was dependent on TNFα and IFNγ, the latter of which was essential for Sca-1 monocyte differentiation. Monocyte recruitment and GC disruption also occurred during LPS-supplemented vaccination and Listeria monocytogenes infection. Thus, systemic activation of the innate immune response upon severe bacterial infection is induced at the expense of antibody-mediated immunity.Copyright © 2022 Elsevier Inc. All rights reserved.
About The Expert
Adi Biram
Jingjing Liu
Hadas Hezroni
Natalia Davidzohn
Dominik Schmiedel
Eman Khatib-Massalha
Montaser Haddad
Amalie Grenov
Sacha Lebon
Tomer Meir Salame
Nili Dezorella
Dotan Hoffman
Paula Abou Karam
Moshe Biton
Tsvee Lapidot
Mats Bemark
Roi Avraham
Steffen Jung
Ziv Shulman
References
PubMed