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Sci Immunol. 2017 Oct 6;2(16). pii: eaah5520. doi: 10.1126/sciimmunol.aah5520.

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

Author information

1
Department of Immunology, University of Connecticut (UConn) Health, Farmington, CT 06030, USA.
2
Center for Quantitative Medicine, UConn Health, Farmington, CT 06030, USA.
3
Department of Cell Biology, UConn Health, Farmington, CT 06030, USA.
4
Department of Pediatrics, UConn Health, Farmington, CT 06030, USA.
5
Institute for Systems Genomics, UConn Health, Farmington, CT 06030, USA.
6
School of Life Science, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan.
7
Department of Immunology, University of Connecticut (UConn) Health, Farmington, CT 06030, USA. kamal.khanna@nyumc.org.

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.

PMID:
28986418
PMCID:
PMC5969998
DOI:
10.1126/sciimmunol.aah5520
[Indexed for MEDLINE]
Free PMC Article

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