Microglia and the control of autoreactive T cell responses

Abstract

Microglial activation is one of the earliest and most prominent features of nearly all CNS neuropathologies often occurring prior to other indicators of overt neuropathology. Whether microglial activation in seemingly healthy CNS tissue during the early stages of several is a response to early stages of neuronal or glial distress or an early sign of microglial dysfunction causing subsequent neurodegeneration is unknown. Here we characterize and discuss how changes in the CNS microenvironment (neuronal activity/viability, glial activation) lead to specific forms of microglial activation. Specifically, we examine the potential role that TREM-2 expressing microglia may play in regulating the effector function of autoreactive T cell responses. Thus, we suggest that ubiquitous suppression of microglial activation during CNS inflammatory disorders rather than targeted manipulation of microglial activation, may in the end be maladaptive leading to incomplete remission of symptoms.

Fig. 1

Microglia in adult murine CNS visualized with tomato lectin.

Fig. 2

Real-time PCR analysis of CXCL14 (A) and protease-nexin 1 (B) in cultured microglia and peritoneal macrophages, untreated or LPS/IFNgamma treated as previously described in Schmid et al. (2002). CXCL14 primers: (forward primer: 5′-ATAAGGGGTTTTGTATTTGTCCAT; reverse primer: 5′-CATGCTCACTGTTCCTCCCA; amplification product: 76 bp), PN-1 primers: (forward primer: 5′-CTGGGATGCTGTAGTGAAGGAT; reverse primer: 5′-CCTGGAAAGTCACACATATCAACA; amplification product: 163 bp).

Fig. 3

Alternative splicing of TREM-2 generates a non-receptor form of the molecule with potential to serve as a “decoy” receptor.