Different activation patterns of mouse primary microglia induced by LPS and poly(I:C). Mus musculus strain:C57BL/6

Microglia are CNS resident innate immune cells that become activated in response to bacteria or viruses. TLRs expressed in microglia are a conserved receptor family that interacts with pathogen-associated molecular patterns and initiates innate immune responses in the brain. Among TLRs, microglia respond strongly to activation of TLR3 and TLR4, which recognize viral dsRNA poly(I:C) and bacterial endotoxin LPS, respectively. However, few studies have thoroughly examined and compared functional phenotypes and downstream mechanisms between LPS- and poly(I:C)-exposed primary microglia. Here, we investigated microglial responses upon LPS and poly(I:C) stimulation by detecting various phenotypes ranging from morphology, proliferation, secretion, chemotaxis, to phagocytosis, as well as explored sequential gene expression and signal cascades. Interestingly, we found that microglial activation pattern induced by LPS distinguished from that induced by poly(I:C). Regarding microglial morphology, LPS caused an ameboid shape while poly(I:C) induced a bushy shape. Microglial proliferation was also facilitated by LPS but not by poly(I:C). In addition, LPS enhanced chemotactic migration towards C5a and phagocytosis of synaptosomes in microglia, while these functions were suppressed by poly(I:C). Furthermore, genome-wide analysis provided gene-level support to these functional differences between LPS- and poly(I:C)-stimulated microglia, which may be associated with NF-kb and type I interferon pathways. Altogether, this study extends our understanding of TLR roles in microglia and provides insights into selecting proper inflammatory microglial models, which may facilitate the identification of new targets for therapeutic application.