FcγRI (CD64): an identity card for intestinal macrophages

Abstract

Macrophages are becoming increasingly recognized as key cellular players in intestinal immune homeostasis. However, differentiating between macrophages and dendritic cells (DCs) is often difficult, and finding a specific phenotypic signature for intestinal macrophage identification has remained elusive. In this issue of the European Journal of Immunology, Tamoutounour et al. [Eur. J. Immunol. 2012. 42: 3150-3166] identify CD64 as a specific macrophage marker that can be used to discriminate DCs from macrophages in the murine small and large intestine, under both steady-state and inflammatory conditions. The authors also propose a sequential 'monocyte-waterfall' model for intestinal macrophage differentiation, with implications for immune tolerance and inflammation at the gut mucosal interface. This Commentary will discuss the advantages and potential limitations of CD64 as a marker for intestinal macrophages.

Figure 1. MF differentiation in the intestinal lamina propria

(A) ‘Mo-waterfall’ model (based on FACS plot pattern): Ly6C^hi blood monocytes (Mo) enter the intestinal lamina propria (LP) where they downregulate Ly6C and acquire the expression of MHC-II and CD64, becoming macrophages (MF). (B) Left: under steady state conditions, Mo enter to the LP in a CCR2-dependent manner. They first go through P1/P2 stages (CD64^low/+F4/80^negCX3CR1^−/int) to finally become P3/P4 tolerogenic IL-10-producing MF (CD64⁺F4/80⁺CX3CR1^high). Right: during inflammation MF differentiation is blunted, reaching only the P2-MF stage and becoming pro-inflammatory iNOS⁺TNFα⁺ MF. In this setting there is also massive P2-MF infiltration in mesenteric lymph nodes (MLN), which might also depend on CCR2.