Research ArticleMACROPHAGES

CD169+ macrophages orchestrate innate immune responses by regulating bacterial localization in the spleen

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Science Immunology  06 Oct 2017:
Vol. 2, Issue 16, eaah5520
DOI: 10.1126/sciimmunol.aah5520

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Positioning sentinels

Immune cells in the marginal zone of the spleen, particularly marginal zone macrophages, play a critical role in detecting and capturing blood-borne pathogens. Here, Perez et al. have examined the role of CD169+ splenic marginal zone macrophages in priming antibacterial responses. Selective deletion of CD169+ macrophages using a diphtheria toxin–based depletion system severely impaired the ability of mice to clear Listeria monocytogenes. By tracking L. monocytogenes and immune cells, they show that CD169+ macrophages cooperate with splenic dendritic cells to transport bacteria from the marginal zone to the T cell zone to prime immune responses to Listeria. The study illustrates the importance of splenic architecture in containing initial pathogen dissemination and in shaping antimicrobial responses.

Abstract

The spleen is an important site for generating protective immune responses against pathogens. After infection, immune cells undergo rapid reorganization to initiate and maintain localized inflammatory responses; however, the mechanisms governing this spatial and temporal cellular reorganization remain unclear. We show that the strategic position of splenic marginal zone CD169+ macrophages is vital for rapid initiation of antibacterial responses. In addition to controlling initial bacterial growth, CD169+ macrophages orchestrate a second phase of innate protection by mediating the transport of bacteria to splenic T cell zones. This compartmentalization of bacteria within the spleen was essential for driving the reorganization of innate immune cells into hierarchical clusters and for local interferon-γ production near sites of bacterial replication foci. Our results show that both phases of the antimicrobial innate immune response were dependent on CD169+ macrophages, and, in their absence, the series of events needed for pathogen clearance and subsequent survival of the host was disrupted. Our study provides insight into how lymphoid organ structure and function are related at a fundamental level.

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