Nod1 signaling overcomes resistance of S. pneumoniae to opsonophagocytic killing.
Nod1 signaling overcomes resistance of S. pneumoniae to opsonophagocytic killing.
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DOI：
10.1371/journal.ppat.0030118
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发表时间：
2007-08-24
期刊：
影响因子：
6.7
通讯作者：
Weiser JN
中科院分区：
文献类型：
--
作者：
Lysenko ES;Clarke TB;Shchepetov M;Ratner AJ;Roper DI;Dowson CG;Weiser JN
由革兰氏阳性病原体肺炎链球菌（Sp）引起的气道感染导致中性粒细胞的募集，但这些细胞的细菌杀伤有限。在小鼠模型中，Sp和革兰氏阴性种流感嗜血杆菌（Hi）的共定植提供了足够的刺激，诱导中性粒细胞和补体介导的Sp从粘膜表面清除。Hi的产物，而不是Sp的产物，也能促进体外富集中性粒细胞的腹膜渗出细胞杀死Sp。在这里，我们确定Hi的刺激是它的肽聚糖。通过核苷酸结合寡聚化结构域-1 （Nod1）的信号传导促进了调节自噬细胞杀伤的增强，该结构域参与识别Hi细胞壁中含有的γ- d -谷氨酰胺-中二氨基苯甲酸（meso-DAP），而不是Sp。用Hi或含有meso-DAP的化合物（包括合成肽聚糖片段）处理小鼠的中性粒细胞显示出以Nod1依赖的方式增加Sp杀伤。此外，Nod1−/−小鼠在共定植过程中显示出降低的hi诱导的Sp清除率。这些观察结果提供了对微生物竞争机制的深入了解，并证明了Nod1在中性粒细胞介导的体内细菌清除中的重要性。病原体一般在实验室里一次研究一种。然而，大多数细菌生存在复杂的环境中，它们不仅要适应宿主，还要适应微生物群落的其他成员。利用小鼠共定殖模型，我们已经证明一种细菌（流感嗜血杆菌）可以利用其宿主的先天免疫反应来竞争并消灭居住在上呼吸道相同微环境中的另一种细菌（肺炎链球菌）。这种作用的分子机制涉及识别流感嗜血杆菌上发现的细胞壁片段，而不是肺炎链球菌。对这种免疫刺激片段的反应需要Nod1，这是一种宿主分子，在对细菌细胞壁的特定肽的反应中传递炎症信号。这种nod1介导的炎症刺激触发一种白细胞（中性粒细胞）吞噬并杀死肺炎链球菌的能力增加，有效地将其从宿主气道粘膜表面的壁龛中清除。因此，我们的研究证明了Nod1在中性粒细胞介导的细菌感染清除中的重要性。此外，我们还描述了微生物之间通过选择性刺激宿主先天免疫反应而发生的种间竞争机制。
Airway infection by the Gram-positive pathogen Streptococcus pneumoniae (Sp) leads to recruitment of neutrophils but limited bacterial killing by these cells. Co-colonization by Sp and a Gram-negative species, Haemophilus influenzae (Hi), provides sufficient stimulus to induce neutrophil and complement-mediated clearance of Sp from the mucosal surface in a murine model. Products from Hi, but not Sp, also promote killing of Sp by ex vivo neutrophil-enriched peritoneal exudate cells. Here we identify the stimulus from Hi as its peptidoglycan. Enhancement of opsonophagocytic killing was facilitated by signaling through nucleotide-binding oligomerization domain-1 (Nod1), which is involved in recognition of γ-D-glutamyl-meso-diaminopimelic acid (meso-DAP) contained in cell walls of Hi but not Sp. Neutrophils from mice treated with Hi or compounds containing meso-DAP, including synthetic peptidoglycan fragments, showed increased Sp killing in a Nod1-dependent manner. Moreover, Nod1−/− mice showed reduced Hi-induced clearance of Sp during co-colonization. These observations offer insight into mechanisms of microbial competition and demonstrate the importance of Nod1 in neutrophil-mediated clearance of bacteria in vivo. Pathogens are generally studied in the laboratory one species at a time. Most exist, however, in complex environments where they must adapt not only to their host but also to other members of the microbial flora. Using a mouse model of co-colonization, we have shown that one bacterial species (Haemophilus influenzae) can take advantage of the innate immune response of its host to outcompete and eliminate another species (Streptococcus pneumoniae) that resides in the same microenvironment of the upper respiratory tract. The molecular mechanism for this effect involves recognition of a cell wall fragment found on H. influenzae, but not on S. pneumoniae. The response to this immunostimulatory fragment requires Nod1, a host molecule that transmits inflammatory signals in response to specific peptides of the bacterial cell wall. This Nod1-mediated inflammatory stimulation triggers an increase in the ability of a type of white blood cell (neutrophil) to engulf and then kill S. pneumoniae, effectively removing it from its niche on the mucosal surface of the host airway. Our study, therefore, provides a demonstration of the importance of Nod1 in neutrophil-mediated clearance of bacterial infection. In addition, we have described a mechanism for interspecies competition between microbes that occurs through selective stimulation of host innate immune responses.
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影响因子：
6.7
作者：
Lysenko ES;Ratner AJ;Nelson AL;Weiser JN
通讯作者：
Weiser JN
影响因子：
3.1
作者：
Kadioglu, A;Gingles, NA;Andrew, PW
通讯作者：
Andrew, PW
影响因子：
3.6
作者：
Lysenko, E;Richards, JC;Weiser, JN
通讯作者：
Weiser, JN
影响因子：
3.6
作者：
Crisostomo, M. Ines;Vollmer, Waldemar;Tomasz, Alexander
通讯作者：
Tomasz, Alexander
影响因子：
6.4
作者：
Gould, JM;Weiser, JN
通讯作者：
Weiser, JN