Ciccarelli Emma Jo, Bendelstein Moshe, Yamamoto Katerina K, Reich Hannah, Savage-Dunn Cathy
Department of Biology, Queens College, CUNY, Flushing NY.
PhD Program in Biology, The Graduate Center, CUNY, New York NY.
bioRxiv. 2024 Feb 14:2023.03.06.531324. doi: 10.1101/2023.03.06.531324.
Host response to pathogens recruits multiple tissues in part through conserved cell signaling pathways. In , the bone morphogenetic protein (BMP) like DBL-1 signaling pathway has a role in the response to infection in addition to other roles in development and post-developmental functions. In the regulation of body size, the DBL-1 pathway acts through cell autonomous signal activation in the epidermis (hypodermis). We have now elucidated the tissues that respond to DBL-1 signaling upon exposure to two bacterial pathogens. The receptors and Smad signal transducers for DBL-1 are expressed in pharyngeal muscle, intestine, and epidermis. We demonstrate that expression of receptor-regulated Smad (R-Smad) gene in the pharynx is sufficient to improve the impaired survival phenotype of mutants and that expression of in the intestine has no effect when exposing worms to bacterial infection of the intestine. We also show that two antimicrobial peptide genes - and - are regulated by DBL-1 signaling through R-Smad SMA-3 activity in the pharynx. Finally, we show that pharyngeal pumping activity is reduced in mutants and that other pharynx-defective mutants also have reduced survival on a bacterial pathogen. Our results identify the pharynx as a tissue that responds to BMP signaling to coordinate a systemic response to bacterial pathogens.
宿主对病原体的反应部分通过保守的细胞信号通路募集多个组织。在[具体内容缺失]中,骨形态发生蛋白(BMP)样DBL-1信号通路除了在发育和发育后功能中的其他作用外,在对感染的反应中也发挥作用。在体型调节中,DBL-1通路通过表皮(皮下组织)中的细胞自主信号激活起作用。我们现在已经阐明了在暴露于两种细菌病原体时对DBL-1信号作出反应的组织。DBL-1的受体和Smad信号转导子在咽肌、肠道和表皮中表达。我们证明,在咽部表达受体调节型Smad(R-Smad)基因足以改善[具体基因缺失]突变体受损的存活表型,并且当将线虫暴露于肠道细菌感染时,在肠道中表达[具体基因缺失]没有效果。我们还表明,两个抗菌肽基因——[具体基因缺失]和[具体基因缺失]——在咽部通过R-Smad SMA-3活性受DBL-1信号调节。最后,我们表明[具体基因缺失]突变体的咽部抽吸活动减少,并且其他咽部缺陷突变体在细菌病原体上的存活率也降低。我们的结果确定咽部是一个对BMP信号作出反应以协调对细菌病原体的全身反应的组织。