Splenic marginal zone CD169+ macrophages are critical for regulating host response to Staphylococcus aureus infection 3196

Abstract Description CD169+ macrophages are a specialized subset of tissue-resident macrophages located in the splenic marginal zone (MZ) and are recognized as key frontline defenders against pathogens, particularly the intracellular gram-positive bacterium Listeria monocytogenes (LM). While their crucial role in orchestrating innate immune responses and facilitating bacterial clearance during LM infections is well-documented, their involvement in combating gram-positive extracellular bacteria, such as Staphylococcus aureus—a major cause of sepsis—remains largely unexplored. Here, we present novel findings demonstrating that CD169+ macrophages are essential for effective clearance of S. aureus and host survival. Utilizing CD169-DTR mice for selective depletion of CD169+ macrophages, we reveal that the absence of these macrophages permits S. aureus to leverage its quorum-sensing mechanisms, inducing a robust inflammatory response within the spleen and impairing neutrophil-mediated bacterial clearance. Our study sheds new light on the critical role of CD169+ macrophages in managing extracellular bacterial infections in vivo and suggests potential therapeutic approaches that target these macrophages to enhance treatment outcomes for S. aureus infections. Funding Sources NIH R01AI143861 Topic Categories Innate Immune Responses and Host Defense: Cellular Mechanisms (INC)