Alternatively activated macrophages in infection and autoimmunity
Introduction
A number of excellent reviews have been written in the past few years describing macrophage activation and polarization (see [1], [2], [3], [4]). The aim of this review is to highlight the role of infection and tissue damage in directing macrophage phenotype and the impact polarized macrophage populations have on the initiation and propagation of autoimmune diseases. The influence of sex hormones on macrophage polarization and function will also be examined. Most of the discussion of alternatively activated macrophages in this review will focus on research conducted in animal models.
Section snippets
Classification of macrophages
Macrophages are innate immune cells that play a key role in normal tissue homeostasis, presentation of foreign and self antigens following infection or injury, pathogen clearance, resolution of inflammation and wound healing [1], [2], [5], [6], [7]. Following antigen stimulation immature monocytes emigrate from blood vessels into peripheral tissues where they differentiate into mature macrophages and dendritic cells (DCs) comprising as much as 15% of total cells [1], [7]. Macrophages are
Infection and injury in AD
For some time infections have been postulated to play a role in the initiation and/or promotion of autoimmune diseases (ADs). The role of infection has been difficult to substantiate for a number of reasons. Many of the infections suspected to cause ADs are widespread in the population, such as coxsackievirus or cytomegalovirus, and often an active infection can no longer be detected by the time the signs and symptoms of AD appear [29]. Several theories have been proposed to explain
M2 and autoimmune diseases
Although the hallmark of AD is the generation of autoantigen-specific T and B cell responses, macrophages and neutrophils comprise the majority of the infiltrate during the peak of acute inflammation [42], [72]. Other factors critical in determining the development of AD include genetic background and sex [31], [42], [45], [53], [73]. For example, BALB/c mice develop predominant Th2 and M2 responses following infection or adjuvant inoculation compared to C57BL/6 mice due to their high numbers
Concluding remarks
Alternatively activated macrophages are induced by the Th2-type cytokines IL-4 and IL-13 and are well known for their ability to inhibit proinflammatory responses by the release of IL-10 and TGF-β. M2 and MDSCs are also induced in response to viral and bacterial infections usually associated with Th1 or Th17-type responses, such as CVB3, M. tuberculosis and CFA supplemented with M. tuberculosis and pertussis toxin that is used to induce AD in animal models (Table 1). Recent findings in animal
Acknowledgements
Work discussed in this review was supported by NIH R01 grants HL087033 (D.F.) and HL67290, HL70729 and a Fellowship Grant from the Myocarditis Foundation (D.C.).
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