Impaired activation of the innate immune response to bacterial challenge in Tourette syndrome

Abstract

Objectives: Infections resulting in immune activation have been proposed to play an etiological role in a subgroup of patients with Tourette syndrome (TS).

Methods: In order to further characterize the interaction between pathogens and the innate immune system the toll-like receptor (TLR) 4 on CD14 + monocytes and soluble CD14 (sCD14) levels were analyzed in the serum of 33 Tourette patients and 31 healthy controls. Moreover, collected blood samples were stimulated with lipopolysaccharide (LPS) mimicking a bacterial infection. TLR4 was analysed by flow cytometry, sCD14 was analysed by enzyme-linked immunosorbent assay.

Results: Patients had a lower receptor expression of TLR4 after stimulation with LPS (P = 0.045) and higher levels of sCD14 (unstimulated P = 0.014, after LPS P = 0.045). The increase in TLR4 expression after stimulation with LPS was significantly higher in the control group (P = 0.041).

Conclusions: Higher levels of sCD14, lower levels of TLR4 expression after stimulation and a diminished up-regulation of TLR4 expression after LPS stimulation in patients might represent an impaired activation of the innate immune response in TS, especially in regard to bacterial infection. The impaired response to pathogens could eventually lead to a higher susceptibility for infections. Recurring infections and a chronic inflammation could trigger and maintain the symptoms of TS.

Keywords: Tourette syndrome; innate immunity; monocytes; soluble CD14; toll-like receptor.