Center for Pulmonary and Infectious Disease Control.
J Infect Dis. 2014 Feb 15;209(4):578-87. doi: 10.1093/infdis/jit495. Epub 2013 Sep 16.
Previously, we found that interleukin 22 (IL-22) inhibits intracellular growth of Mycobacterium tuberculosis in human monocyte-derived macrophages (MDMs). In the current study, we determined the mechanisms underlying these effects. We found that W7, a phagolysosomal fusion inhibitor, abrogates IL-22-dependent M. tuberculosis growth inhibition in MDMs, suggesting that IL-22 acts through enhanced phagolysosomal fusion. Our microarray analysis indicated that recombinant IL-22 (rIL-22) enhances the expression of an intracellular signaling molecule, calgranulin A. This was confirmed by real-time polymerase chain reaction, Western blot, and confocal microscopy. Calgranulin A small interfering RNA (siRNA) abrogated rIL-22-dependent growth inhibition of M. tuberculosis in MDMs. IL-22 enhanced Rab7 expression and downregulated Rab14 expression of M. tuberculosis-infected MDMs, and these effects were reversed by calgranulin A siRNA. These results suggest that M. tuberculosis growth inhibition by IL-22 depends on calgranulin A and enhanced phagolysosomal fusion, which is associated with increased Rab7 and reduced Rab14 expression.
先前，我们发现白细胞介素 22（IL-22）能够抑制人单核细胞来源的巨噬细胞（MDM）中的结核分枝杆菌的细胞内生长。在本研究中，我们确定了这些作用的机制。我们发现，噬溶酶体融合抑制剂 W7 可消除 IL-22 依赖性 MDM 中结核分枝杆菌生长的抑制作用，表明 IL-22 通过增强噬溶酶体融合起作用。我们的微阵列分析表明，重组白细胞介素 22（rIL-22）增强了细胞内信号分子钙粒蛋白 A 的表达。实时聚合酶链反应、Western blot 和共聚焦显微镜证实了这一点。钙粒蛋白 A 小干扰 RNA（siRNA）消除了 rIL-22 对 MDM 中结核分枝杆菌生长的抑制作用。IL-22 增强了感染结核分枝杆菌的 MDM 中的 Rab7 表达，并下调了 Rab14 的表达，而钙粒蛋白 A siRNA 则逆转了这些作用。这些结果表明，IL-22 通过钙粒蛋白 A 和增强的噬溶酶体融合抑制结核分枝杆菌的生长，这与 Rab7 表达增加和 Rab14 表达减少有关。
