BCG 접종 후 발생한 화농성 림프절염 환자의 단핵구에서 Toll-like receptor 2의 발현 = Toll-like receptor 2 expression on monocytes from patients with BCG vaccine-associated suppurative lymphadenitis

다국어 초록 (Multilingual Abstract)

Purpose : Toll-like receptor 2 (TLR2) is critical in the immune response to mycobacterial infections. The purpose of this study was to analyze TLR2 surface expressions and TLR2-mediated tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) production in patients with BCG vaccine-associated suppurative lymphadenitis.
Methods : Peripheral monocytes were separated from 16 patients with BCG vaccine-associated suppurative lymphadenitis and 10 healthy controls using a magnet cell isolation kit. Monocytes (1×106 cells/well) were incubated with a constant amount of Pam3CSK4 (100 µg/mL) for 24 hours. TLR2 surface expression on monocytes was analyzed by FACS analysis and TLR-2 mRNA expression was determined by RT-PCR. TLR2-mediated TNF-α and IL-6 production were measured by ELISA.
Results : In patients with BCG vaccine-associated suppurative lymphadenitis, low TLR2 expression on monocytes (3.39±1.2% versus 4.64±2.6%) together with significantly lower TLR2 mRNA expression than in the healthy controls was seen after Pam3CSK4 stimulation. TLR2-mediated TNF-α and IL-6 production in patients with BCG vaccine-associated suppurative lymphadenitis (TNF-α, 775.5±60.8 pg/mL; IL-6, 4,645.8±583.9 pg/mL) were also lesser than that in healthy controls (TNF-α, 1,098.5±94.3 pg/mL; IL-6, 6,696.3±544.3 pg/mL).
Conclusion : These findings suggest that low TLR2 expression on monocytes might be associated with increased susceptibility to BCG vaccine-associated suppurative lymphadenitis.

국문 초록 (Abstract)

목 적 : TLR2는 숙주의 항결핵 방어면역의 중요한 역할을 하는 것으로 알려져 있다. 본 연구는 BCG 접종 후 발생한 화농성 림프절염 환자 단핵구에서 TLR2의 발현과 TLR2 리간드 자극에 의한 TNF-α와 IL-6의 생성을 조사하여 화농성 림프절염 발병과 TLR2의 연관성을 알아보고자 하였다.
방 법 : BCG 접종 후 발생한 화농성 림프절염 환자 16명과 건강 대조군 10명의 말초 혈액에서 단핵구를 분리하고, TLR2 리간드인 Pam3CSK4로 자극한 후 유세포분석과 역전사중합효소반응을 이용하여 TLR2의 발현을 측정하였고, 자극 후 TNF-α와 IL-6의 생성을 측정하여 TLR2의 발현 정도를 간접적으로 조사하였다.
결 과 : BCG 접종 후 발생한 화농성 림프절염 환자 단핵구의 TLR2 발현 정도(3.39±1.2%)는 대조군(4.64±2.6%)에 비하여 유의하게 감소하였고, 단핵구 자극에 의한 TNF-α와 IL-6의 생성도 대조군(TNF-α, 1,098.5±94.3 pg/mL; IL-6, 6,696.3±544.3 pg/mL)에 비하여 환자군(TNF-α, 775.5±60.8 pg/mL; IL-6, 4,645.8±583.9 pg/mL)에서 유의하게 감소하였다. 그리고 자극 시간에 따른 TLR2 발현 정도와 TNF-α와 IL-6의 생성 증가가 유사한 양상을 나타내었다.
결 론 : 본 연구의 결과에서 BCG 접종 후 발생한 화농성 림프절염 환자군 단핵구의 TLR2 발현 감소가 연관되어 있고, M. bovis BCG의 리간드 인식에 TLR2가 관여함을 추정할 수 있다.

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