IL-33 and M2a alveolar macrophages promote lung defense against the atypical fungal pathogen Pneumocystis murina.
IL-33 and M2a alveolar macrophages promote lung defense against the atypical fungal pathogen Pneumocystis murina.
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DOI：
10.4049/jimmunol.1002558
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发表时间：
2011-02-15
期刊：
影响因子：
--
通讯作者：
Steele C
中科院分区：
文献类型：
--
作者：
Nelson MP;Christmann BS;Werner JL;Metz AE;Trevor JL;Lowell CA;Steele C
我们最近报道，缺乏髓系Src家族酪氨酸激酶Hck、Fgr和Lyn （Src三重敲除[TKO]）的小鼠对鼠肺囊虫的先天肺清除率增加，这与这些小鼠的肺泡巨噬细胞（AMs）杀死鼠肺囊虫的能力提高有关。在本文中，我们表明，尽管具有增强的杀伤作用，但来自幼年Src TKO小鼠的AMs并未表现出对P. murina的增强炎症反应。我们随后发现，与野生型小鼠相比，感染P. murina的Src TKO小鼠的AMs和肺部表达的M2a标记物RELM-α和Arg1以及M2a相关的趋化因子CCL17和CCL22的水平显著更高。促进M2a极化的主要细胞因子IL-4和IL-13在野生型和Src TKO小鼠的肺中没有差异。Src - TKO小鼠感染P. murina导致新型IL-1家族细胞因子IL-33的肺生成增加。肺组织中IL-33的免疫组化分析显示其主要定位于肺泡上皮细胞的细胞核。我们进一步证明，与未经处理的AMs相比，未经处理的AMs对M2a的实验极化能更有效地杀死鼠p.m urina，并通过添加IL-33进一步增强。给C57BL/6小鼠注射IL-33增加了肺部RELM-α和CCL17水平，增强了P. murina的清除，尽管对肺部的细胞组成没有影响。综上所述，这些结果表明M2a am是抗鼠假体的有效效应细胞。此外，增强M2a极化可能是治疗肺囊虫病的辅助疗法。
We have recently reported that mice deficient in the myeloid Src-family tyrosine kinases Hck, Fgr, and Lyn (Src triple knockout [TKO]) had augmented innate lung clearance of Pneumocystis murina that correlated with a higher ability of alveolar macrophages (AMs) from these mice to kill P. murina. In this article, we show that despite possessing enhanced killing, AMs from naive Src TKO mice did not demonstrate enhanced inflammatory responses to P. murina. We subsequently discovered that both AMs and lungs from P. murina-infected Src TKO mice expressed significantly greater levels of the M2a markers RELM-α and Arg1, and the M2a-associated chemokines CCL17 and CCL22 than did wild-type mice. IL-4 and IL-13, the primary cytokines that promote M2a polarization, were not differentially produced in the lungs between wild-type and Src TKO mice. P. murina infection in Src TKO mice resulted in enhanced lung production of the novel IL-1 family cytokine IL-33. Immunohistochemical analysis of IL-33 in lung tissue revealed localization predominantly in the nucleus of alveolar epithelial cells. We further demonstrate that experimental polarization of naive AMs to M2a resulted in more efficient killing of P. murina compared with untreated AMs, which was further enhanced by the addition of IL-33. Administration of IL-33 to C57BL/6 mice increased lung RELM-α and CCL17 levels, and enhanced clearance of P. murina, despite having no effect on the cellular composition of the lungs. Collectively, these results indicate that M2a AMs are potent effector cells against P. murina. Furthermore, enhancing M2a polarization may be an adjunctive therapy for the treatment of Pneumocystis.
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影响因子：
15.3
作者：
MACKANESS, G B
通讯作者：
MACKANESS, G B
影响因子：
4.4
作者：
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4.4
作者：
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DOI：
10.1165/rcmb.2004-0300oc
发表时间：
2005-06-01
影响因子：
6.4
作者：
Evans, SE;Hahn, PY;Limper, AH
通讯作者：
Limper, AH