Alternatively Activated Macrophages in Types 1 and 2 Diabetes

Arlett Espinoza-Jiménez,Luis I Terrazas,Alberto N Peón

doi:10.1155/2012/815953

Abstract

Macrophages are innate immune cells derived from monocytes, which, in turn, arise from myeloid precursor cells in the bone marrow. Macrophages have many important roles in the innate and adaptive immune response, as well as in tissue homeostasis. Two major populations have been defined: The classically activated macrophages that respond to intracellular pathogens by secreting proinflammatory cytokines and reactive oxygen species and alternatively activated macrophages which are induced during Th2 responses displaying anti-inflammatory activities. Both macrophage populations are central players in diabetes, the first one triggering inflammatory responses which initiates insulitis and pancreatic β cell death during type 1 diabetes, whereas the second population decreases hyperglycemia, insulitis, and inflammation in the pancreas, thereby negatively regulate type 1 diabetes. Obesity is an important factor in the development of type 2 diabetes; classically activated macrophages are a dominant cell population involved in the establishment of the inflammatory profile, insulin resistance, and activation of inflammatory signals during the development and progression of this disease. In contrast, alternatively activated macrophages regulate the release of proinflammatory cytokines, attenuating adipose tissue inflammation. Here, we review the advantages and disadvantages of these two macrophage populations with regard to their roles in types 1 and 2 diabetes.

Highlights

Mφs have important roles in the immune response and tissue homeostasis
We have shown that previous Taenia crassiceps infection of diabetic mice, which were induced by multiple low doses of streptozotocin (MLD-STZ), significantly decreased the incidence of type 1 diabetes (T1D), hyperglycemia, and the inflammatory infiltration of islets of Langerhans
TNF-α has the ability to reduce the expression of important genes in the glucose regulation process, such as the glucose transporter GLUT-4 [4]; TNF-α receptor knock out mice are resistant to diabetes induction [69], suggesting that the endocrine function of adipose tissue (AT) is important in the recruitment and activation of CAMφs and the induction of insulin resistance

Summary

Macrophages

Mφs have important roles in the immune response and tissue homeostasis. The huge capacity of Mφs for phagocytosis renders them effective at microbial killing and the clearance of apoptotic and necrotic cells, and through their expression of MHC-II molecules and secretion of pro- and antiinflammatory cytokines, they can trigger CD4+ T-cell activation and differentiation into Th1, Th2, Th17, and Treg subsets [1,2,3]. CAMφs are induced by stimulation with Th1-cell-derived IFN-γ and microbial products, such as bacterial lipopolysaccharide (LPS) [5], and respond to microbial infection with an enhanced phagocytic microbicidal capability through the expression of the CAMs marker, inducible nitric oxide synthase (iNOS), which catalyzes the conversion of L-arginine into ROS, such as NO. These macrophages produce several proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), interleukin-12 (IL-12), IL-1β, and IL-23, as well as toxic mediators, such as reactive oxygen species (ROS) and nitric oxide (NO), through the expression of inducible nitric oxide synthase (iNOS). This paper focuses on the different roles that CAMφs and AAMφs display in both types of diabetes, emphasizing the role of AAMφs as essential players in diabetes regulation

Diabetes Mellitus

Findings

Conclusions