Role of Monocytes and Intestinal Macrophages in Crohnʼs Disease and Ulcerative Colitis

Abstract

Monocytes and macrophages are part of the body's first line of defence, eliminating pathogens by phagocytosis or by releasing a broad array of inflammatory mediators, such as cytokines, chemokines, and proteases. In humans, 3 subsets of monocytes are described in blood with seemingly different functions, the classical (CD14CD16) monocytes, the intermediate (CD14CD16) monocytes, and the nonclassical (CD14CD16) monocytes. In the intestine, macrophages can be divided into resident and inflammatory macrophages that are distinguished by low and high expression of CD14, respectively. However, the roles and function of the 3 monocyte subsets in health and disease are not fully understood. In this review, we describe what is known about the origin of human intestinal macrophages and their blood monocytic counterparts and many of their numerous distinct mechanisms influencing the intestinal immune system.

Larval Echinococcus multilocularis infection reduces dextran sulphate sodium‐induced colitis in mice by attenuating T helper type 1/type 17‐mediated immune reactions

“…54,55 However, in IBD, the recruitment of inflammatory monocytes into damaged tissue frequently worsens the inflammation. 56 Macrophages from E. multilocularis-infected mice have been shown to exhibit a reduced ability to present a conventional antigen, such as ovalbumin to specific responder lymph node T cells, when compared with normal macrophages from non-infected mice; this triggers an unresponsiveness of T cells, which in turn leads to the suppression of their clonal expansion during the chronic phase of E. multilocularis infection. 57 High periparasitic nitric oxide production by peritoneal exudate cells, mainly macrophages, were also shown to contribute to E. multilocularis-induced immunosuppression.…”

Alteration of glucocorticoid receptors and exacerbation of inflammation during lytic cytomegalovirus infection in THP‐1 cells

“…However, some studies insist CMV is merely a ‘bystander’ during UC . Alterations in pro‐ and anti‐inflammatory cytokines secreted by monocytes and macrophages play a role in the course of UC . Furthermore, CMV infection can also induce CMV‐related colitis.…”

“…During CMV reactivation, the immediate early gene (IE1) initiates viral replication and is a marker for lytic infection. In active ulcerative colitis (UC), monocytes and macrophages infiltrate intestinal lesions . THP‐1 cells derived from a patient with acute monocytic leukaemia share similar features with human monocytic cells.…”

Crohn’s Disease Patients with Depression Exhibit Alterations in Monocyte/Macrophage Phenotype and Increased Proinflammatory Cytokine Production

“…Psychological stress activates mobilization and infiltration of monocytes into the brain where they differentiate into proinflammatory microglia, a specialized form of macrophage in the nervous system [12]. In humans, intestinal macrophages exclusively originate from peripheral blood monocytes, which consist of 3 subsets with distinct phenotypes as well as seemingly different functions: The classical subset (CD14++CD16-), the intermediate subset (CD14++CD16+), and the nonclassical subset (CD14+CD16++) [13,14]. In CD patients, the proportion of classical monocytes is found to be decreased, while the proportion of intermediate monocytes is increased and that of the nonclassical subtype is unaltered [15].…”

“…In CD patients, the proportion of classical monocytes is found to be decreased, while the proportion of intermediate monocytes is increased and that of the nonclassical subtype is unaltered [15]. Both macrophages and their monocytic counterparts have long been identified as key players of immune dysregulation, which is one of the fundamental mechanisms of inflammatory bowel disease [13].…”