The identification and developmental requirements of colonic CD169⁺ macrophages

Abstract

SummaryCD169-positive macrophages in the marginal zone of the spleen and subcapsular sinus of lymph nodes play an important role as gatekeepers, strategically located to capture pathogens. Here we identified a population of CD169-positive macrophages in the colon and investigated which factors influenced their development. Murine colonic CD115 + F4/80 lo CD11c lo macrophages expressing CD169 were present in the lamina propria, mainly surrounding the crypts. In spite of the high levels of bacterial flora in the colon and the importance of Toll-like receptor signalling in mucosal homeostasis, the presence of CD169 + macrophages was not affected in mice that were deficient in MyD88-mediated Toll-like receptor signalling and in mice in which the bacterial flora was eradicated. Whereas the development of splenic CD169 + macrophages was dependent on lymphotoxin a, colonic CD169 + macrophages were present in normal numbers in lymphotoxin a-deficient mice. In contrast, reduced numbers of CD169 + macrophages were found in the colon of mice deficient in vitamin A, whereas CD169 + macrophages in the spleen were unaffected. In conclusion, we identified a new macrophage subset in the lamina propria of the colon characterized by the expression of CD169. Its differentiation, unlike CD169 + macrophages in lymphoid organs, is independent of lymphotoxin a signalling, but requires vitamin A.

Barrier-tissue macrophages: functional adaptation to environmental challenges

“…Mφs are found in a number of locations within the mucosa itself, ranging from immediately next to the basement membrane underlying the epithelium to the central core of the LP, and at different positions along the villus-crypt axis (Figure 2A). A specific population expressing CD169 is found near the crypt base, close to the submucosa and these may have distinct functions and developmental requirements 51,52 . Substantial numbers of mφs are also found in the external muscularis layer of the intestine ( Figure 1A).…”

“…Although mature resident mφs do not become proinflammatory during experimental colitis induced by chemicals or T cells 14,16,18 , this can occur under conditions when inflammation occurs in the absence of IL10 mediated control of mφ activity 21,128 . One population of resident mφs that may contribute directly to inflammation is that expressing CD169, which recruits monocyte neutrophils via production of CCL8 51,52 . Furthermore, muscularis mφs play important roles in postoperative paralytic ileus by producing nitric oxide in response to local trauma, leading to activation of neighbouring neurons 54 .…”

Commensal microbiota drive the functional diversification of colon macrophages

“…13 Finally, CD169 + macrophages have also been described in the colon, their differentiation in the steady-state dependent on Vitamin A, and during intestinal inflammation secrete CCL8 to recruit inflammatory monocytes. 14,15 Resident intestinal MPs are thought to play an essential role in killing invading microbes, clearing dead and dying cells, control of intestinal inflammation, and contributing to wound healing and epithelial repair, 16,17 and they are highly phagocytic and bactericidal cells that respond to TLR ligands with the production of IL-10, and other anti-inflammatory, but low levels of inflammatory cytokines, 5,8,[18][19][20] and also have been reported to be important in the expansion or survival of regulatory T cells within the lamina propria through their production of IL-10 during steady state and colitis. 21,22 Several tissue-specific factors affecting intestinal MP identity and function have been described, including retinoic acid, microbial metabolites, TGFβ, and IL-10, however, other influences on intestinal MP phenotype are largely unknown.…”

Deficiency of the B Cell-Activating Factor Receptor Results in Limited CD169+ Macrophage Function during Viral Infection

“…Lymphotoxin signaling is critical for CD169 ϩ cell development in spleen and lymph node tissues (32,38,39,41). Moreover, it has been shown that lymphotoxins are derived from B cells, which are important for maintenance of CD169 ϩ cells (29,39).…”

“…6A). These data suggest that impaired B cell numbers in Baffr Ϫ/Ϫ mice may contribute to insufficient lymphotoxin expression to maintain normal levels of CD169 ϩ cells (29,38,41,42). To investigate the role of lymphotoxin beta during enforced viral replication, we infected Ltb fl/fl ϫ CD19-Cre ϩ animals and compared them to their corresponding controls.…”