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.