- 學位論文
肺結核病人單核球細胞對結核分枝桿菌抗原呈現的研究
The research of mycobacterium tuberculosis antigen presentation by monocytes from tuberculosis patients
摘要
本研究目的是想探討肺結核 (TB) 病人其單核球細胞對於分枝結核桿菌的抗原呈現能力是否有缺陷，另外也探討維他命D在防禦分枝結核桿菌感染的角色。病人及測試者共分為3個群組: (1) 活動性TB病人，(2) 已經痊癒的TB病人，及(3) 經常接觸TB患者的人 (例如醫療相關工作者)。在單核球對分枝結核桿菌的抗原呈現能力實驗結果，我們發現經常接觸TB患者的人抗原呈現能力明顯地高於活動性TB病人和已經痊癒的TB病人，但活動性TB病人和已經痊癒的TB病人這兩個群組，抗原呈現能力並沒有差異。另外許多論文報導關於維他命D可以預防感染TB，根據我們實驗的結果發現，維他命D對經常接觸TB患者的人，可以增加其單核球細胞對分枝結核桿菌抗原呈現的能力。但對活動性TB病人和已經痊癒的TB病人而言，維他命D並不會增加其單核球細胞對分枝結核桿菌抗原呈現的能力。因此研究的初步發現有2點: (1)會得到TB的人 (包括活動性TB病人和已痊癒的TB病人)，其單核球對分枝結核桿菌的抗原呈現能力可能有缺陷，而導致TB感染。(2) 維他命D對經常接觸TB的人，可以增加對抵抗感染TB的能力。但對TB的病人 (包括活動性TB病人和已痊癒的TB病人)，維他命D的防禦角色並沒有明顯功能。另外我們進一步分析活動性TB病人和經常接觸TB患者的人這兩個族群。我們發現，活動性TB病人組單核球的1-α hydroxylase (CYP27B1)活性較經常接觸TB患者的人明顯地高。活動性TB病人組的單核球若以分枝結核桿菌的抗原去刺激，1,25(OH)2D3明顯地下降。但相對地，經常接觸TB患者的人，1,25(OH)2D3並沒有明顯的變化。因此我們推論，單核球可能是1-α hydroxylase產生的另一個來源處，可以將25-hydroxyvitamin D3轉換成有活性的1,25(OH)2D3.
並列摘要
To determine whether there were any defects in the presentation of the Mycobacterium tuberculosis antigen by monocytes from patients with tuberculosis (TB) and the role of vitamin D in the defense against M. tuberculosis. A prospective study aimed at analyzing the presentation of the M. tuberculosis antigen by monocytes and the response to vitamin D treatment in three groups of participants: (1) those with active TB, (2) those with healed TB and (3) those with frequent TB contact. The antigen presentation ability of monocytes of persons in the frequent contact group was significantly higher than that of the active TB and healedTB groups. There was no difference between patients with active and healed TB. In addition, 1,25(OH)2D3 increased the presentation of mycobacterial antigens by monocytes from participants with frequent TB contact, but not those with active or healed TB. Patients with active and healed TB exhibit defective M. tuberculosis presentation in monocytes. The administration of vitamin D did not correct this defect in monocytes from participants with active or healed TB, but could increase antigen presentation by monocytes in participants with frequent TB contact. In addition, we performed further studies to determine whether monocytes are alternative sites of 1,25(OH)2D3 conversion beyond renal tubular cells. Using an ex vivo bioassay, in this study, we found that 1-α hydroxylase (CYP27B1) activity in monocytes is significantly higher in patients with active TB (tuberculosis) than in those with frequent TB contact. However, when monocytes from patients with active TB were re-stimulated with antigen derived from Mycobacterium tuberculosis, less 1,25(OH)2D3 was observed. In contrast, the level of 1,25(OH)2D3 was unchanged in those with frequent TB contact. We conclude that monocytes may be an alternative source of 1-α hydroxylase that could convert 25-hydroxyvitamin D3 to the more active 1,25(OH)2D3.