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Challenge with innate and protein antigens induces CCR7 expression by microglia in vitro and in vivo
I M Dijkstra1, A H de Haas, N Brouwer
1Department of Medical Physiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Abstract:
Since activated microglia are able to phagocytose damaged cells and subsequently express major histocompatibility complex class II (MHC-II) and co-stimulatory proteins, they are considered to function as antigen presenting cells (APCs) in the central nervous system. The maturation and migratory potential of professional APCs is associated with the expression of chemokine receptor CCR7. We therefore investigated whether the immunological activation of microglia induces CCR7 expression. We here present that activation of cultured microglia by both the innate antigen lipopolysaccharide and protein antigen ovalbumin rapidly induces CCR7 expression, accompanied by increased MHC-II expression. Moreover, it is shown that CCR7 expression in IBA-1 positive cells is induced during the symptom onset and progression of experimental autoimmune encephalomyelitis, a rodent model for multiple sclerosis. These results suggest that microglia express CCR7 under specific inflammatory conditions, corroborating the idea that microglia develop into APCs with migratory potential toward lymphoid chemokines.
Insights
Activated microglia express CCR7, a receptor linked to cell migration, when stimulated by antigens or during experimental autoimmune encephalomyelitis. This suggests microglia can act as antigen-presenting cells (APCs) with the potential to travel to lymphoid organs.
Area of Science:
- Neuroimmunology
- Cellular immunology
Background:
- Microglia, the resident immune cells of the central nervous system (CNS), act as antigen-presenting cells (APCs) by phagocytosing damaged cells and expressing MHC-II and co-stimulatory molecules.
- The chemokine receptor CCR7 is crucial for the maturation and migration of professional APCs.
Purpose of the Study:
- To investigate whether immunological activation of microglia induces the expression of CCR7.
- To determine if microglia acquire APC characteristics with migratory potential.
Main Methods:
- Cultured microglia were activated using lipopolysaccharide (LPS) and ovalbumin (OVA).
- CCR7 and MHC-II expression was analyzed in activated microglia.
- CCR7 expression was examined in IBA-1 positive cells during experimental autoimmune encephalomyelitis (EAE).
Main Results:
- Microglial activation by LPS and OVA rapidly induced CCR7 expression.
- Increased MHC-II expression was observed concurrently with CCR7 induction.
- CCR7 expression was detected in microglia during the onset and progression of EAE.
Conclusions:
- Microglia express CCR7 under specific inflammatory conditions, particularly during EAE.
- These findings support the concept that microglia can develop into APCs with migratory capabilities towards lymphoid chemokines.
- Microglial CCR7 expression indicates a role in neuroinflammatory processes and immune surveillance within the CNS.
