Pertussis toxin stimulates IL-17 production in response to Bordetella pertussis infection in mice.
Pertussis toxin stimulates IL-17 production in response to Bordetella pertussis infection in mice.
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DOI：
10.1371/journal.pone.0007079
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发表时间：
2009-09-17
期刊：
影响因子：
3.7
通讯作者：
Carbonetti NH
中科院分区：
文献类型：
--
作者：
Andreasen C;Powell DA;Carbonetti NH
在百日咳博德特氏菌呼吸道感染的小鼠模型中，细菌在第一周内在气道中繁殖，然后在接下来的3 - 4周内被宿主免疫反应清除。百日咳毒素（PT）是一种仅由百日咳博德特氏菌分泌的毒力因子，它通过抑制和调节宿主免疫反应促进细菌在气道中的生长。通过比较野生型和PT缺陷型菌株，我们研究了PT在调节小鼠百日咳博德特氏菌感染期间影响中性粒细胞募集的气道细胞因子和趋化因子反应中的作用。我们发现，尽管PT早期抑制中性粒细胞募集，但在野生型菌株感染后4天，大量中性粒细胞被募集到气道，而PT缺陷型菌株则没有，并且这与吸引中性粒细胞的趋化因子基因表达上调相关。此外，表达细胞因子白细胞介素 - 17A（IL - 17）、肿瘤坏死因子 - α和干扰素 - γ的基因也有类似的上调，表明是一种混合的Th1/Th17反应。参与Th17诱导的细胞因子白细胞介素 - 6的表达比IL - 17反应更早地上调。我们表明，PT而非细菌数量对这些反应的诱导很重要。流式细胞术分析显示，产生IL - 17的细胞是巨噬细胞、中性粒细胞以及T细胞，并且主要存在于气道而非肺组织中。IL - 17的抗体中和显著降低了趋化因子基因表达和中性粒细胞向气道的募集，但仅略微增加了细菌载量峰值。这些数据表明，在小鼠百日咳博德特氏菌感染期间，PT通过诱导包括IL - 17在内的与Th1和Th17相关的细胞因子刺激炎症反应，但IL - 17在预防感染中的作用仍有待确定。
In a mouse model of respiratory tract infection by Bordetella pertussis, bacteria multiply in the airways over the first week and are then cleared over the next 3–4 weeks by the host immune response. Pertussis toxin (PT), a virulence factor secreted exclusively by B. pertussis, promotes bacterial growth in the airways by suppression and modulation of host immune responses. By comparison of wild type and PT-deficient strains, we examined the role of PT in modulating airway cytokine and chemokine responses affecting neutrophil recruitment during B. pertussis infection in mice. We found that, despite early inhibition of neutrophil recruitment by PT, high numbers of neutrophils were recruited to the airways by 4 days post-infection with the wild type strain, but not with the PT-deficient strain, and that this correlated with upregulation of neutrophil-attracting chemokine gene expression. In addition, there was similar upregulation of genes expressing the cytokines IL-17A (IL-17), TNF-α and IFN-γ, indicating a mixed Th1/Th17 response. Expression of IL-6, a cytokine involved in Th17 induction, was upregulated earlier than the IL-17 response. We showed that PT, rather than bacterial numbers, was important for induction of these responses. Flow cytometric analysis revealed that the IL-17-producing cells were macrophages and neutrophils as well as T cells, and were present predominantly in the airways rather than the lung tissue. Antibody neutralization of IL-17 significantly reduced chemokine gene expression and neutrophil recruitment to the airways, but only modestly increased peak bacterial loads. These data indicate that PT stimulates inflammatory responses by induction of Th1- and Th17-associated cytokines, including IL-17, during B. pertussis infection in mice, but a role for IL-17 in protection against the infection remains to be established.
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DOI：
10.1084/jem.20070663
发表时间：
2007-08-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Annunziato F;Cosmi L;Santarlasci V;Maggi L;Liotta F;Mazzinghi B;Parente E;Filì L;Ferri S;Frosali F;Giudici F;Romagnani P;Parronchi P;Tonelli F;Maggi E;Romagnani S
通讯作者：
Romagnani S
影响因子：
3.1
作者：
Fedele, G;Stefanelli, P;Ausiello, CM
通讯作者：
Ausiello, CM
影响因子：
4.4
作者：
Lentschat, A;Karahashi, H;Arditi, M
通讯作者：
Arditi, M
影响因子：
4.9
作者：
Gaffen, Sarah L
通讯作者：
Gaffen, Sarah L
影响因子：
4.4
作者：
Iwamoto, Sanju;Iwai, Shin-ichi;Miyazaki, Akira
通讯作者：
Miyazaki, Akira