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The Role of Macrophages in Immune Responses to Giardia

巨噬细胞在贾第鞭毛虫免疫反应中的作用

基本信息

批准号：
10860555
负责人：
STEVEN M SINGER
金额：
$ 15.88万
依托单位：
GEORGETOWN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-07-01 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10860555
关键词：
Anti-Inflammatory Agents Bacteria Biological Assay Bone Marrow C57BL/6 Mouse Celiac Disease Cells Chemosensitization Child Chimera organism Chronic Cognitive Crohn&apos s disease Cyst Data Defect Dendritic Cells Development Diagnosis Diarrhea Diphtheria Toxin Enteral Flow Cytometry Food Hypersensitivity Galactosamine Galactose Binding Lectin Giardia Giardia lamblia Histologic Human IL17 gene Immune response Immune system Immunity Immunoglobulin A In Vitro Incidence Infection Inflammation Inflammatory Ingestion Innate Immune Response Interleukin-10 Intestines Kinetics Laboratories Lectin Life Macrophage Malabsorption Syndromes Measures Mediating Microbe Modeling Monitor Morbidity - disease rate Mus Nutrient Osteomyelitis Outcome Parasites Pathology Patients Peritoneal Macrophages Peroxidases Persons Play Polymers Procedures Production Proliferating Quantitative Reverse Transcriptase PCR Reporter Research Training Role Severity of illness Signal Pathway Signal Transduction Small Intestines Supervision Syndrome Therapeutic Toxoplasma Toxoplasma gondii Transgenic Mice United States Work adaptive immune response bioluminescence imaging cell type co-infection cytokine diarrheal disease doctoral student enteric pathogen gut inflammation immunoregulation in vivo in vivo imaging inhibitor insight low and middle-income countries monocyte mortality mouse model oral infection pathogen response transmission process undergraduate student vaccine development

项目摘要

Abstract Giardia lamblia is the most common protozoan cause of diarrhea in the world. It infects ~500 million people worldwide, often resulting in nutrient malabsorption which can lead to physical and cognitive developmental defects in children. Paradoxically, recent data also indicate that the presence of Giardia is associated with reduced levels of moderate-to-severe diarrhea in children. The infection is transmitted by ingestion of cysts and the cyst wall contains large amounts of N-acetyl galactosamine (GalNAc) polymer. The macrophage galactose-binding lectin (MGL) is the dominant lectin capable of recognizing GalNAc. Our hypothesis is that recognition of cyst wall material by MGL plays a significant role in determining the outcome of infections by modulating both innate and adaptive immune responses. Specifically, we hypothesize that stimulation of macrophages through MGL1 potentiates the production of IL-10 in response to other activating signals such as the presence of bacteria. This IL-10 may enhance parasite persistence, but also limits pathology and decreases disease severity. We will address these hypotheses utilizing in vitro cultures of macrophages derived from MGL1 deficient mice. We will also analyze infections with Giardia, alone and in combination with another parasite known to induce severe inflammatory pathology in mice, using mice deficient in MGL1 as well as mice lacking macrophages. We will assay the parasite burdens and markers of pathology during infections. Bone marrow chimeras will be used to identify roles of MGL1 on specific cell types.

摘要贾第虫是世界上最常见的引起腹泻的原生动物。它感染了~ 5亿世界各地的人们，往往导致营养吸收不良，这可能导致身体和认知儿童的发育缺陷。巧合的是，最近的数据也表明，贾第虫的存在是与儿童中度至重度腹泻水平降低有关。感染是通过食入包囊后，包囊壁含有大量的N-乙酰半乳糖胺（GalNAc）聚合物。的巨噬细胞半乳糖结合凝集素（MGL）是能够识别GalNAc的主要凝集素。我们假设MGL对囊壁物质识别在决定结果中起重要作用通过调节先天性和适应性免疫反应来控制感染。具体来说，我们假设，通过MGL 1刺激巨噬细胞可增强IL-10的产生，信号，如细菌的存在。这种IL-10可以增强寄生虫的持久性，但也限制了病理学和降低疾病的严重程度。我们将利用体外培养来解决这些假设，来自MGL 1缺陷小鼠的巨噬细胞。我们还将分析贾第虫感染，单独和与另一种已知在小鼠中诱导严重炎症病理学的寄生虫组合，使用小鼠缺乏MGL 1的小鼠以及缺乏巨噬细胞的小鼠。我们将分析寄生虫负荷和感染期间的病理学。骨髓嵌合体将用于鉴定MGL 1对特定细胞类型的作用。

项目成果

期刊论文数量（13）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Stool antigen immunodetection for diagnosis of Giardia duodenalis infection in human subjects with HIV and cancer.

粪便抗原免疫检测用于诊断 HIV 和癌症患者十二指肠贾第鞭毛虫感染。

DOI：
10.1016/j.mimet.2017.07.004
发表时间：
2017
期刊：
Journal of microbiological methods
影响因子：
2.2
作者：
Nooshadokht,Maryam;Kalantari-Khandani,Behjat;Sharifi,Iraj;Kamyabi,Hossein;Liyanage,NamalPM;Lagenaur,LaurelA;Kagnoff,MartinF;Singer,StevenM;Babaei,Zahra;Solaymani-Mohammadi,Shahram
通讯作者：
Solaymani-Mohammadi,Shahram

Recent advances in the Giardia-host relationship reveal danger lurking behind the smile.

贾第鞭毛虫与宿主关系的最新进展揭示了微笑背后潜藏的危险。