Figure legends
Figure 1 Macrophage origin, differentiation and plasticity.Macrophages may originate both at the prenatal stage from the yolk sac and fetal liver, and during the postnatal stage from the bone marrow via CCL2/CCR2 axis. In specific tissue contexts, macrophages are programmed by local factors. Here they may be both long-lived self-renewing cells or replenished from the blood monocyte pool. The macrophage activation states in tissues can be loosely equated to macrophages in disease tissues, but they are heterogeneous in origin and phenotypically plastic, with variable contributions to disease progression. They show an alternatively activated M2 phenotype in the repair phase and could substitute the tissue resident macrophages.
Figure 2. Role of macrophages in association with microbiota in maintaining intestinal barrier function. During homeostasis in the lamina propria, cross-talk between resident intestinal macrophages and regulatory T cells (Treg) results in IL-10 and TGF-β production that helps to maintain the intact intestinal epithelial cell (IEC) barrier with tight junction (TJ) proteins. Intestinal lumen is mainly populated with healthy microbiota in homeostasis. In diseases conditions, intestinal recruited macrophages show an pro-inflammatory phenotype with release of TNF-α, iNOS, IL-1β , IL-6 and IL-18 which further damages the IEC barrier. However, if this acquired phenotype is due to phagocytosis of specific dysbiotic microbial products, is yet to be studied. In addition, macrophages that phagocytose apoptotic IEC release chemokines like CL2, CCL7, CXCL1 and 2, which recruits further neutrophils and monocytes into intestinal tissues. At this phase, the intestinal lumen observed with dysbiosis, apoptotic IEC and damaged IEC barrier with loss of TJ proteins, leading to translocation of microbial products and pro-inflammatory mediators into lamina propria and eventually to systemic circulation promoting systemic inflammation and distinct organ damage. During repair phase, macrophage acquire a pro-repair phenotype and release various tissue repair mediators including TGF-β, PDGF, IGF, VEGF and IL-10 along with proposed repair mediators like Granulin and Plet1. These mediators resolve the inflammation and repair IEC barrier by expression of TJ proteins and regulate the intestinal barrier function. However, if this acquired phenotype is due to phagocytosis of specific pro-repair microbial products, is yet to be studied.