Macrophages in gastrointestinal homeostasis and inflammation

Abstract

Monocyte-derived mononuclear phagocytes, particularly macrophages, are crucial to maintain gastrointestinal homeostasis in the steady state but are also important for protection against certain pathogens. However, when uncontrolled, they can promote immunopathology. Broadly two subsets of macrophages can be considered to perform the vast array of functions to complete these complex tasks: resident macrophages that dominate in the healthy gut and inflammation-elicited (inflammatory) macrophages that derive from circulating monocytes infiltrating inflamed tissue. Here, we discuss the features of resident and inflammatory intestinal macrophages, complexities in identifying and defining these populations and the mechanisms involved in their differentiation. In particular, focus will be placed on describing their unique ontogeny as well as local gastrointestinal signals that instruct specialisation of resident macrophages in healthy tissue. We then explore the very different roles of inflammatory macrophages and describe new data suggesting that they may be educated not only by the gut microenvironment but also by signals they receive during development in the bone marrow. Given the high degree of plasticity of gut macrophages and their multifaceted roles in both healthy and inflamed tissue, understanding the mechanisms controlling their differentiation could inform development of improved therapies for inflammatory diseases such as inflammatory bowel disease (IBD).

<p>Functional aspects, phenotypic heterogeneity, and tissue immune response of macrophages in infectious diseases</p>

“…23 In the intestine, macrophages recognize and remove enteric pathogens and maintain the balance necessary for the operation of the microbiota. 23,[26][27][28] The spleen contains macrophage lines derived to perform diverse functions. Splenic macrophages are responsible for phagocytizing senescent or altered erythrocytes, capturing antigens, and processing and presenting them to T lymphocytes.…”

S100A8/A9 modulates inflammatory collateral tissue damage during intraperitoneal origin systemic candidiasis

“…Macrophages are sentinels for immune signaling that leads to leukocytosis but may cause problems when uncontrolled (35). The pro-inflammatory cytokine response of WT and S100A9 -/- was determined using bone marrow-derived macrophages (BMDMs) to monitor the ability of primary macrophages to induce TNFα (Fig.…”

Immunology of Gut-Bone Signaling

“…In addition to neutrophils, IBD pathology is also associated with an influx of lymphocytes into the mucosa (156). These cells produce vast quantities of pro-inflammatory cytokines (41,42,158). Increased activation especially of the IL-1 pathway is more active during the onset of inflammation rather than during the sustained phase, especially in the colon (42).…”

“…Increased activation especially of the IL-1 pathway is more active during the onset of inflammation rather than during the sustained phase, especially in the colon (42). Members of the IL-12 family of heterodimeric cytokines including IL-12, IL-23, IL-27, and IL-35 have been shown to be upregulated in antigen presenting cells (42,158), while TNFα has been shown to be enhanced in mononuclear cells. The effects of TNF are suggested to be two-fold; promoting inflammation by binding to its receptors, as well as causing cell death through activation of receptor-interacting protein kinase 1 and caspase 3 proteins (42,158).…”