Expression Patterns of TLR Complex Components Within Trigeminal Sensory Neurons

Objective: To determine the expression patterns of Toll-like receptor (TLR) membrane signalling complex components within specific, neurochemically identified trigeminal ganglion (TG) neuronal populations. It has recently been shown that activation of TLRs on nociceptors can induce both the production of pro-inflammatory mediators and sensitisation of the thermal transducer protein TRPV1. There is little current data describing the expression of co-receptor components and intracellular transduction proteins in trigeminal sensory neurons. This will help to understand potential mechanisms of neuronal sensitisation following oral infection. 

Method: Immunohistochemistry was used to investigate the expression patterns of the following molecules within the TG; TLR4, the adapter protein MyD88 and two isoforms of a phospholipid metabolising enzyme (LPCAT), previously shown to be involved in the immune response to lipopolysaccharide (LPS). Co-localisation compared the expression patterns of TLR4, MyD88, LPCAT1 and LPCAT2 with the neurochemical markers Neurofilament-200, TRPV1 and isolectin B₄. Co-immunoprecipitation was performed to investigate the composition of the TLR membrane signalling complex with emphasis on the involvement of either MD-1 or MD-2.

Result: Results indicate that both TLR4 and MyD88 are expressed in small/medium diameter neurons suggesting a preferential expression by nociceptors. LPCAT1 shows a similar expression pattern whereas LPCAT2 was only observed in non-neuronal cells. 

Conclusion: This is the first time to our knowledge that LPCAT1 and LPCAT2 expression has been described in trigeminal sensory neurons. The presence of TLR4 and MyD88 in trigeminal nociceptors supports previous evidence and outlines a potential innate immune function of the sensory nervous system whereby bacteria interact directly with nociceptors to induce the production of inflammatory mediators and contribute towards a heightened pain phenotype. Further work will investigate the signalling pathways employed by neuronal TLRs in response to ligand exposure and the functional outcomes in terms of trigeminal sensory neuronal activation/sensitisation.