Autocrine IL-10 induces hallmarks of alternative activation in macrophages and suppresses antituberculosis effector mechanisms without compromising T cell immunity.
Autocrine IL-10 induces hallmarks of alternative activation in macrophages and suppresses antituberculosis effector mechanisms without compromising T cell immunity.
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DOI：
10.4049/jimmunol.0803567
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发表时间：
2009-07-15
期刊：
影响因子：
--
通讯作者：
Hölscher C
中科院分区：
文献类型：
--
作者：
Schreiber T;Ehlers S;Heitmann L;Rausch A;Mages J;Murray PJ;Lang R;Hölscher C
IL-10升高与再活化结核（TB）有关。由于巨噬细胞而不是T细胞是结核中IL-10的主要来源，我们分析了巨噬细胞特异性过表达IL-10在气溶胶感染结核分枝杆菌（Mtb）后转基因小鼠（macil -10转基因）中的后果。macil -10转基因小鼠比非转基因小鼠更容易感染慢性结核分枝杆菌，感染12周后肺部细菌载量更高，死亡时间明显早于对照组。巨噬细胞来源的IL-10不影响TH1细胞的分化、募集和激活以及ifn - γ依赖性效应基因对Mtb的诱导。然而，肺基因表达的微阵列分析揭示了在mtb感染的macil -10转基因小鼠中过度代表的替代性巨噬细胞激活的特征模式。重要的是，精氨酸酶-1基因的表达和活性在转基因小鼠中显著增强，同时活性氮中间体的产生减少。此外，il -10依赖性精氨酸酶-1诱导降低了巨噬细胞的抗分枝杆菌效应机制。总之，巨噬细胞衍生的IL-10触发了替代巨噬细胞激活的各个方面，并促进结核分枝杆菌的复发，而不依赖于对抗结核T细胞免疫的明显影响。
Elevated IL-10 has been implicated in reactivation tuberculosis (TB). Since macrophages rather than T cells were reported to be the major source of IL-10 in TB, we analyzed the consequences of a macrophage-specific overexpression of IL-10 in transgenic mice (macIL-10-transgenic) after aerosol infection with Mycobacterium tuberculosis (Mtb). MacIL-10-transgenic mice were more susceptible to chronic Mtb infection than non-transgenic littermates, exhibiting higher bacterial loads in the lung after 12 weeks of infection and dying significantly earlier than controls. The differentiation, recruitment and activation of TH1 cells as well as the induction of IFN-gamma-dependent effector genes against Mtb were not affected by macrophage-derived IL-10. However, microarray analysis of pulmonary gene expression revealed patterns characteristic of alternative macrophage activation that were overrepresented in Mtb-infected macIL-10-transgenic mice. Importantly, arginase-1 gene expression and activity were strikingly enhanced in transgenic mice accompanied by a reduced production of reactive nitrogen intermediates. Moreover, IL-10-dependent arginase-1 induction diminished anti-mycobacterial effector mechanisms in macrophages. Together, macrophage-derived IL-10 triggers aspects of alternative macrophage activation and promotes Mtb recrudescence independent of overt effects on anti-TB T cell immunity.
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影响因子：
15.3
作者：
D'Andrea, A;Aste-Amezaga, M;Valiante, N M;Ma, X;Kubin, M;Trinchieri, G
通讯作者：
Trinchieri, G
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
3.1
作者：
Hölscher, C;Mohrs, M;Brombacher, F
通讯作者：
Brombacher, F
影响因子：
15.3
作者：
Cooper, AM;Magram, J;Ferrante, J;Orme, IM
通讯作者：
Orme, IM
影响因子：
4.4
作者：
Hölscher, C;Arendse, B;Brombacher, F
通讯作者：
Brombacher, F