Innate immune response to microbial PAMPs in the schistosome-transmitting snail,

血吸虫传播蜗牛对微生物 PAMP 的先天免疫反应，

• 批准号: 8230339
• 负责人: JOHN T. SULLIVAN
• 金额: $ 29.67万
• 依托单位: UNIVERSITY OF SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-03-01 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8230339
• 关键词: Asexual Reproduction; Biomphalaria; Cell division; Complex; DNA; Development; Escherichia coli; Fresh Water; Gene Expression Profile; Genes; Gram-Negative Bacteria; Hematopoiesis; Hematopoietic; Immune; Immune response; Immune system; Injection of therapeutic agent; Invertebrates; Larva; Lead; Lipid A; Lipopolysaccharides; Measurement; Microarray Analysis; Mitotic; Mitotic Activity; Molecular; Organ; Outcome; Parasites; Parasitic Diseases; Pattern; Pattern recognition receptor; Peptidoglycan; Phagocytes; Polysaccharides; RNA; Reporting; Research; Resistance; Scanning; Schistosoma; Schistosome Parasite; Schistosomiasis; Snails; Sporocysts; System; Testing; Time; immune function; insight; microbial; pathogen; response; transcriptomics; vector

DESCRIPTION (provided by applicant): Compatibility between schistosomes and their snail intermediate hosts is determined in part by the outcome of the interaction of the larval parasite with the host's innate internal defense system (IDS). As in other innate immune systems, the IDS of the vector snail Biomphalaria glabrata is thought to rely on recognition of pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs). However, both the PAMPs and PRRs important in schistosome-snail interactions are not well understood. The specific aims of the proposed research are to identify one or more specific PAMPs to which the IDS of B. glabrata responds, and then to characterize this response at the transcriptomic level. Recently, a mitotic response to injected crude lipopolysaccharide (LPS) from Escherichia coli has been observed in the hematopoietic amebocyte-producing organ (APO) of schistosome-resistant (but not schistosome- susceptible) B. glabrata, and the pattern of mitotic activity is quite similar to that previously described against injected schistosome extracts. This observation provides an opportunity to identify for the first time a specific PAMP that triggers an immune response in a schistosome-transmitting snail. Should this mitotic activity in fact be directed against LPS, it represents a unique invertebrate response against one of the best characterized microbial PAMPs, and identification of the responsible PAMP(s) may provide insights on recognition of incompatible schistosome larvae by the snail IDS, which presumably evolved largely in response to microbial pathogens long before the recent acquisition of schistosome parasites. The proposed research will test the mitogenic activity of the most likely candidate PAMPs found in crude LPS (i.e., LPS, peptidoglycan, unmethylated CpG-rich DNA), and if activity is associated with LPS itself, then the active component of LPS (i.e., lipid A or the O polysaccharide) will be identified. These studies will utilize histological analysis of cell division in APOs of injected snails. Finally, with the use of microarray analysis, the pattern of gene expression in the APO in response to injection with the active bacterial PAMP will be compared to that previously reported in response to other forms of nonself. PUBLIC HEALTH RELEVANCE: The capacity for a snail to serve as an intermediate host for medically important digenetic trematodes hinges in part on the interaction of the parasite with the host's innate immune system. The proposed research seeks to identify for the first time a specific bacterial molecule that triggers an innate immune response (hematopoiesis) in the schistosome-transmitting snail, Biomphalaria glabrata, and then to characterize the pattern of gene expression in response to this molecule. Results of this study may provide new information on immune recognition of bacterial molecular patterns, as well as insights on the underlying mechanisms of snail-schistosome compatibility.

描述(由申请人提供)：血吸虫和它们的蜗牛中间宿主之间的兼容性部分取决于幼虫与宿主的固有内部防御系统(IDS)相互作用的结果。与其他先天性免疫系统一样，媒介钉螺的入侵检测系统被认为依赖于模式识别受体(PRRs)对病原体相关分子模式(PAMPs)的识别。然而，PAMPs和PRRs在血吸虫-钉螺相互作用中的重要性还不是很清楚。这项研究的具体目的是确定光滑假单胞菌的入侵检测系统对一个或多个特定的PAMP作出反应，然后在转录水平上描述这种反应。最近，在抗血吸虫(但对血吸虫不敏感)的光滑小球虫的造血祖细胞产生器官(APO)中观察到了对注射的大肠杆菌粗脂多糖(LPS)的有丝分裂反应，并且有丝分裂的活动模式与先前描述的针对注射的血吸虫提取物的有丝分裂活动非常相似。这一观察为首次识别在传播血吸虫的蜗牛中触发免疫反应的特定PAMP提供了机会。如果这种有丝分裂活性真的是针对脂多糖，它代表了一种独特的无脊椎动物对一种特征最好的微生物PAMP的反应，而责任PAMP的识别(S)可能为蜗牛入侵系统识别不相容的血吸虫幼虫提供了见解，据推测，在最近获得血吸虫寄生虫之前很久，蜗牛入侵系统就已经进化成对微生物病原体的反应了。这项拟议的研究将测试在粗制的脂多糖中发现的最有可能的候选PAMPs(即，脂多糖、肽聚糖、未甲基化的富含CpG的DNA)的有丝分裂活性，如果活性与脂多糖本身有关，则将确定脂多糖的活性成分(即脂类A或O多糖)。这些研究将利用注射蜗牛APO的细胞分裂的组织学分析。最后，利用微阵列分析，将APO中对注射活性细菌PAMP的反应与先前报道的对其他形式的非我反应的基因表达模式进行比较。 公共卫生相关性：蜗牛作为医学上重要的双基因吸虫的中间宿主的能力在一定程度上取决于寄生虫与宿主的先天免疫系统的相互作用。这项拟议的研究旨在首次确定在传播血吸虫的蜗牛中触发先天免疫反应(造血)的特定细菌分子，然后描述对该分子做出反应的基因表达模式。这项研究的结果可能为细菌分子模式的免疫识别提供新的信息，以及对钉螺和血吸虫相容的潜在机制的深入了解。

项目成果

Activation of an innate immune response in the schistosome-transmitting snail Biomphalaria glabrata by specific bacterial PAMPs.

• DOI: 10.1016/j.dci.2013.09.016
• 发表时间: 2014-02
• 期刊: DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
• 影响因子: 2.9
• 作者: Sullivan, John T.;Belloir, Joseph A.
• 通讯作者: Belloir, Joseph A.

Haematopoiesis in molluscs: A review of haemocyte development and function in gastropods, cephalopods and bivalves.

• DOI: 10.1016/j.dci.2015.11.010
• 发表时间: 2016-05
• 期刊: Developmental and comparative immunology
• 影响因子: 2.9
• 作者: Pila EA;Sullivan JT;Wu XZ;Fang J;Rudko SP;Gordy MA;Hanington PC
• 通讯作者: Hanington PC

Fucoidan stimulates cell division in the amebocyte-producing organ of the schistosome-transmitting snail Biomphalaria glabrata.

• DOI: 10.1016/j.jip.2014.09.005
• 发表时间: 2014-11
• 期刊: JOURNAL OF INVERTEBRATE PATHOLOGY
• 影响因子: 3.4
• 作者: Sullivan, John T.;Belloir, Joseph A.;Beltran, Roxxana V.;Grivakis, Aris;Ransone, Kathryn A.
• 通讯作者: Ransone, Kathryn A.