CD169+ marginal zone macrophages are critical for the clearance and localization of listeria monocytogenes following a systemic infection (INC7P.407)

Abstract

Abstract The spleen is a secondary lymphoid organ that plays an important role in providing protection against blood-borne pathogens. CD169+ marginal zone (MZ) macrophages (MZM) are located along the marginal sinus of the spleen and are positioned to be among the first cells to encounter bacteria. However, the precise role of these cells during infection is not well understood. Thus, we used CD169-diptheria toxin receptor (DTR) mice to selectively deplete CD169+ MZM to study the role of CD169+ MZM after Listeria monocytogenes (Lm) infection. CD169+ MZM depleted mice succumbed to sublethal dose of Lm infection due to inefficient capture and unrestricted growth of LM early after infection. In additon, CD169+ MZM depleted mice fail to localize Lm to T cell zones despite greater numbers of replicating bacteria in the MZ and the red pulp early after infection. This suggests CD169+ MZM play a critical role mediating Lm trafficking to T cell zones. The aberrant Lm localization in CD169-DTR mice also resulted in striking disruption of CD11b+ cell granulomas, further increasing bacterial spread to peripheral tissues. Interestingly, CD8α+ dendritic cells (DC) depletion did not rescue the ability of CD169-DTR mice to clear Lm, suggesting that CD169+ MZMs provide an essential route for Lm clearance that precedes the CD8a+ DC infection niche. Thus, our study revealed a novel role of CD169+ MZM as critical mediators of protection against bacterial infections by direct and indirect mechanisms.