Trends in Immunology
ReviewCD169+ macrophages at the crossroads of antigen presentation
Section snippets
Macrophage heterogeneity in secondary lymphoid organs
Macrophages are distributed throughout mouse lymphoid and nonlymphoid tissues. Distinct populations of macrophages can be identified based on the expression of macrophage-specific markers such as F4/80, CD68, SRA-I and CD169, also known as sialoadhesin or sialic acid binding immunoglobulin-like lectin (Siglec) 1 (Table 1) (1). The tissue distribution of other markers expressed by macrophages, such as the mannose receptor (MR; also known as CD206) 2, 3, 4, Marco [5], SIGNR-1 6, 7 and ligands for
CD169+ macrophages and antigen presentation to B cells
It was established more than 15 years ago that MZM macrophages contribute to humoral responses, and in particular, are required for the initiation of antibody responses against T-dependent particulate antigens [26]. The distribution of CD169+ cells alters during the course of an immune response, as determined by staining for MOMA-1 [27] or by detecting ligands for the cysteine-rich domain of the MR [10]. In the course of an immune response, CD169+ cells are found within B cell follicles after
CD169+ macrophages and cross-presentation
Antigen-presenting cells, particularly CD8α+ DCs [30], have developed mechanisms to facilitate the presentation of peptides from internalised material on MHC I, which is essential for the activation of CD8 T cells. Although the cellular mechanisms of this process are not fully understood [31], it is established that CD8 T cells are activated in response to protein antigens both in vivo and in vitro. A greater understanding of this process will facilitate the generation of novel vaccine
Collaboration between CD8α+ DCs and CD169+ macrophages during cross-presentation in spleen
Targeting ovalbumin antigen to MZM macrophages using an anti-CD169 antibody delivered intravenously in the presence of an agonist anti-CD40 antibody as adjuvant [19] promotes CD8 T cell activation to a similar extent as does antigen targeting using DEC205 (CD205) [39], a marker of CD8α+ DCs, the DC subpopulation responsible for cross-presentation. The MZM macrophage-mediated response is protective against challenge with tumour cells that express ovalbumin. Anti-CD169 antibody targeting does not
Direct presentation of dead cell-associated antigens to CD8 T cells by CD169+ macrophages in lymph nodes
Subcutaneous vaccination with irradiated tumour cells activates antigen-specific CD8 T cells to elicit a protective antitumour immune response [32]. This response is not mediated by migratory DCs because injection of dead tumour cells does not induce DC migration (determined by Kaede transgenic mice that express a photoconvertible fluorescent protein [42]), and is not inhibited by the synthetic prostaglandin analogue BW245C, which inhibits skin DC migration [43]. In addition, the response is
Are CD169+ macrophages targets for CD8+ T cells?
Antigen-presenting cells that are capable of activating CD8+ T cells can themselves become targets for elimination. This is considered a mechanism to regulate CD8 responses [47] and can be exploited by pathogens to allow spreading in the host [33]. After infection with P. chabaudi, splenic cells undergo major changes in cellular distribution, and this involves deletion of CD169+ macrophages [34]. CD8+ T cells have been identified as the main cell population responsible for loss of MZM
Concluding remarks
Secondary lymphoid organs are uniquely organised to maximise the induction of acquired immunity through the compartmentalisation of antigen handling and delivery systems that promote effective and selective lymphocyte activation 22, 35. The role selected macrophages play in antigen presentation to naive lymphocytes is only just emerging. In addition to the contribution of CD169+ macrophages to the activation of B cells, iNKT and CD8 T cells, F4/80-expressing macrophages have also been found to
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