CD169+ marginal zone macrophages orchestrate innate immune responses to bacterial infection.

PEREZ O; QIU Z; ROMAGNOLI PA; BENECHET A; MAHER L; TANAKA M; KHANNA KM

Seattle, WA

Congreso; AAI IMMUNOLOGY 2016; 2016

The American Association of Immunologists, Inc.

The spleen is an important site for generating protective immune responses against pathogens. Immune cells in the spleen undergo rapid reorganization to initiate and maintain local inflammatory responses against pathogens. How the spatial dynamics of cellular communication are regulated in the spleen after infection remains unclear. Respectively, CD169+ macrophages are a population of tissue resident macrophages that are positioned in the marginal zone to rapidly encounter invading pathogens. However, the role of splenic CD169+ macrophages during infections is not well understood. Here we show that splenic CD169+ macrophages serve as a primary cellular host to blood-borne bacteria Listeria monocytogens (Lm) and are also essential for the clearance of other bacterial and viral pathogens. In addition to controlling initial bacterial growth, CD169+ macrophages orchestrated a second phase of innate protection by mediating the transport of Lm to the splenic T cell zones and driving the subsequent reorganization of neutrophils, monocytes, and NK cells into hierarchical clusters. Specifically our study revealed that bacterial transport to the T cell zones was mediated by trans-infection of closely interacting CD8 alpha+ DCs with Lm-infected CD169+ macrophages. Although, CD8alpha+ DCs are required for a productive Lm infection in the spleen, to our surprise mice that lacked both CD8alpha+ DCs and CD169+ macrophages were unable to control Lm infection. These results demonstrated that CD169+ macrophages regulated bacterial access to the pathogen favorable CD8+ DC niche, ultimately providing a rationale for reassessing the current paradigm regarding the temporal role of CD8alpha+ DCs during Lm infection.