Type II‐activated macrophages suppress the development of experimental autoimmune encephalomyelitis

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Abstract
Treatment with immune complexes, which ligate Fcγ receptors (FcγRs), suppresses the development of experimental autoimmune encephalomyelitis (EAE). To determine the mechanism of action, we investigated how these immune complexes affected type II activation of macrophages (that is, exposure to immune complexes in a proinflammatory environment). Our results show that lower doses of interferon-γ (IFN-γ) were more effective at priming bone marrow-derived macrophages (BMMφ) to produce more interleukin 10 (IL-10) and less IL-12p40 in response to lipopolysaccharide (LPS) and immune complexes compared with LPS alone. Moreover, at the lowest level of IFN-γ (20 U ml−1), a significant downregulation in the surface expression of CD40, CD80 and PD-L1 was observed in LPS and immune complex-stimulated macrophages (that is, type II activated) than macrophages stimulated with LPS alone (that is, classically activated). Finally, treatment of mice with type II-activated macrophages protected them from developing EAE, suggesting that administration of immune complexes is protective against EAE by inducing type II-activated macrophages.
Funding Information
  • Neurological Foundation of New Zealand (0220PG)
  • Wellington Medical Research Foundation (2001/39)
  • Victoria University of Wellington