Immunolocalization of Toll-like receptors 2 and 4 as well as their endogenous ligand, heat shock protein 70, in rat traumatic brain injury.

OBJECTIVE: Toll-like receptors (TLRs) are essential to the innate immune system for recognizing not only microbial pathogens but also endogenous ligands from injured cells, suggesting that TLRs are a sensitive detection system to tissue injury and play roles in initiating tissue degeneration/regeneration. In this study, the effects of traumatic brain injury (TBI) on lesional expression of TLR2, TLR4, their most common adaptor molecule myeloid differentiation factor 88 (MyD88) and their endogenous ligand, heat shock protein 70 (HSP70), were investigated.
METHODS: Rat TBI was induced using an open-skull weight-drop model. TLR2, TLR4, MyD88 and HSP70 expression was studied by immunohistochemistry.
RESULTS: TLR2, TLR4, HSP70 and MyD88 were mainly found in lesioned regions and subcortical white matter. While infiltration of TLR2+ cells became significant on day 2, significant accumulation of TLR4+, MyD88+ and HSP70+ cells was already seen on day 1, and the numbers of immunopositive cells increased continuously until day 4. Furthermore, double staining together with morphological classification showed that major cellular sources for TLR2, TLR4 and MyD88 were macrophages/microglia in lesioned areas and astrocytes in subcortical white matter. But for HSP70, the major cellular sources were neurons in perilesion and macrophages/microglia in lesion areas and astrocytes in subcortical white matter. DISCUSSION: In summary, our data reveal distinct patterns of localization of TLR+ resident and infiltrating cells in TBI rat brain. Infiltrating activated monocytic cells are the major source of TLR+ cells. These findings warrant further investigation of the roles of TLRs in controlling immune and degenerative/regenerative processes after TBI.