AIDSに合併する結核 : 第75回総会ランチタイムセミナー

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概要

• 論文の詳細を見る

• HIV-1 infection is a major cause of worldwide epidemic of tuberculosis. In Japan, the cumulative number of the patients reported is 131 by the end of 1999 with 10 to 20 annual new cases. Most of Japanese cases are advanced AIDS patients with low CD 4 number less than 100/μ<I>l</I>. The peak age of Japanese patient is 40 to 60 years old, whereas that of foreigners is 20-30 years old, suggesting that most Japanese cases are recurrent tuberculosis. There is increasing clinical evidence that coinfection with <I>M. tuberculosis</I> accelerates progression of AIDS. We found that, <I>in vivo</I>, HIV-1 load and mutation increase in involved lung segments in patients with pulmonary tuberculosis. We also reported that <SUB>Mycobacterium tuberculosis</SUB> stimulates HIV-1 replication by enhancing transcription on the 5 LTR in a macrophage cell line, THP-1, <I>in vitro</I>. In contrast, HIV-1 replication is suppressed by <I>M. tuberculosis</I> infection of monocytes derived macrophages (MDM) or differentiated monocytic THP-1 cells. We observed that HIV-1 5 LTR function was repressed in PMA differentiated THP-1 cells after co-infection with <I>M. tuberculosis</I>. Point mutations in C/EBP-β binding domains of the HIV-1 LTR negative regulatory element (NRE) abolished promoter repression. Monocyte-derived macrophages and differentiated THP-1 cells increased expression of the 16 kDa inhibitory form of C/EBP-β after <I>M. tuberculosis</I> coinfection. Bronchoalveolar lavage cells obtained from normal controls and alveolar macrophages from uninflamed lung of tuberculosis patients also expressed the 16 kDa inhibitory form of C/EBP-β. However, alveolar macrophages from lung segments involved with pulmonary tuberculosis had markedly reduced C/EBP-β expression. These data suggest that 16 kDa isoform of C/EBP-β plays an important role for the control of HIV-1 replication in macrophages. We propose derepression of HIV-1 LTR mediated transcription as one mechanism for enhanced HIV-1 replication observed in pulmonary tuberculosis.

著者

• 本田 芳広

  仙台厚生病院内科

• WEIDEN Michael

  Division of Pulmonary & Critical Care Medicine, New York University Medical Center

• 中田 光

  国際医療センター研究所呼吸器疾患研究部

• 慶長 直人

  国際医療センター研究所呼吸器疾患研究部

• 田中 直彦

  Division of Pulmonary & Critical Care Medicine and Bellevue Chest Service, NYU Medical Center

• 田中 直彦

  Division of Pulmonary & Critical Care Medicine and Bellevue Chest Service, NYU Medical Center

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