Expression of Toll-Like Receptors in the Developing Brain

Abstract

Toll-like receptors (TLR) are key players of the innate and adaptive immune response in vertebrates. The original protein Toll in Drosophila melanogaster regulates both host defense and morphogenesis during development. Making use of real-time PCR, in situ hybridization, and immunohistochemistry we systematically examined the expression of TLR1–9 and the intracellular adaptor molecules MyD88 and TRIF during development of the mouse brain. Expression of TLR7 and TLR9 in the brain was strongly regulated during different embryonic, postnatal, and adult stages. In contrast, expression of TLR1–6, TLR8, MyD88, and TRIF mRNA displayed no significant changes in the different phases of brain development. Neurons of various brain regions including the neocortex and the hippocampus were identified as the main cell type expressing both TLR7 and TLR9 in the developing brain. Taken together, our data reveal specific expression patterns of distinct TLRs in the developing mouse brain and lay the foundation for further investigation of the pathophysiological significance of these receptors for developmental processes in the central nervous system of vertebrates.

Toll-Like Receptor 4 Deficiency Causes Reduced Exploratory Behavior in Mice Under Approach-Avoidance Conflict

“…It is also extensively expressed in the central nervous system [12,28], and its activation has been shown to correlate with many neuropsychiatric conditions including depression and drug addiction [12,29]. TLR4 activation triggers a cascade of signaling events leading to the release of many proinflammatory cytokines.…”

Innate immune responses regulate morphogenesis and degeneration: roles of Toll-like receptors and Sarm1 in neurons

“…Thus, they concluded that the negative effect of R848 is mediated via TLR8 but not TLR7 [31] . However, their results are in conflict to many recent studies from various laboratories regarding the expression of TLR7 in neurons [10,11,20,32] , as evidenced by the results of in situ hybridization, quantitative polymerase chain reaction (Q-PCR), and immunostaining using TLR7 antibodies [10,11,20,32] . Actually, the expression level of TLR7 in neurons is even higher than that of TLR8 [11] .…”

“…Furthermore, Kaul and colleagues performed quantitative PCR to examine the expression levels of TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, and TLR9 in developing brains and found that the levels of TLR7 and TLR9 correlated particularly well with brain development [10] .…”

“…In addition to TLRs, neurons also express the critical TIR domain-containing adaptors, which transduce the downstream signals of TLRs, including myeloid differentiation primary response gene 88 (MyD88), TIR domain-containing adapter-inducing IFN-β (Trif) [10] and sterile alpha and HEAT/Armadillo motif-containing 1 (Sarm1) [12] . Notably, Sarm1 is predominantly expressed in neurons rather than astrocytes, microglia, or the peripheral immune system [12][13][14] .…”

Recognition of pathogen-associated nucleic acids by endosomal nucleic acid-sensing toll-like receptors

“…TLR3 mRNA has also been detected in epithelial cells of many different organs including airway, uterine, corneal, vaginal, biliary, and intestinal organs because the mucous membranes of these organs act as efficient innate barriers to infection from the respiratory tract, and gastrointestinal and urogenital systems [6,16]. Surprisingly, higher expression level of TLR3 is also observed in neurons, astrocytes, and microglia, suggesting a specific function in response to encephalitogenic viruses of the central nervous system [6,17,18]. TLRs 7 and 9 are predominantly expressed in plasmacytoid DCs ( pDCs) in humans and are involved in strong IFN-a induction, but TLR8 tends to be detected in human monocytes and mDCs, and predisposes the induction of inflammatory cytokines [1,[19][20][21][22][23].…”