Generating Innate Immune Diversity to Recognize Newly Emerging Pathogens

产生先天免疫多样性以识别新出现的病原体

• 批准号: 436250-2013
• 负责人: Palaniyar, Nades
• 金额: $ 2.19万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=574326
• 关键词: Generating; Innate; Immune; Diversity; Recognize

. Overview: Emergence of new and drug-resistant pathogens is a reality. Most of these pathogens contain thick carbohydrate coats that are rarely recognized by our classical antibodies (e.g., IgG). However, innate immune collectins are anti-carbohydrate antibody-like molecules, and readily recognize a range of microbes. We will determine whether tissue inflammation induces mutation in collectins such as lung surfactant proteins A and D (SP-A, SP-D), so that the mutant proteins can recognize and neutralize newly emerging pathogens. This mechanism could give an evolutionary advantage to the host animals and humans. Objectives: The objective of this project is to determine whether infection and inflammation generate a repertoire of "anti-carbohydrate antibodies" from innate immune collectin genes. Collectins or collagenous lectins have fibrillar collagen-like regions and globular carbohydrate-recognition domains (CRDs or lectin domains). These collectins bind carbohydrate moieties present on microbial surfaces and neutralize their infectivity. However, collectins are encoded by single copy genes, and do not undergo gene rearrangements or somatic mutations. Therefore, unlike antibodies, these genes do not have the classical ability to generate variant collectins. We will determine whether deamination of specific bases of mRNA results in the generation of point mutations in collectins during inflammation. New knowledge & potential outcome: Findings from this basic science study could represent a paradigm shift in the field of immunology. Our work will show whether the innate immune system instantly changes collectins SP-A and SP-D so that the mutant proteins can recognize newly emerging pathogens and prevent infectious diseases such as pneumonia (e.g., bacteria, virus, fungi). This mechanism could help to stop the emergence of new strains of influenza flu and multi-drug resistant pathogens. Our data will show whether the inflammation is a "necessary evil" during the fight against the newly emerging microbial pathogens, and that suppressing inflammation would weaken the ability of the host to fight against dangerous pathogens.

。概述：出现新的和耐药病原体是一个现实。大多数这些病原体含有厚厚的碳水化合物外壳，很少被我们的经典抗体（例如IgG）识别。然而，先天免疫集合素是抗碳水化合物抗体样分子，并且很容易识别一系列微生物。我们将确定组织炎症是否会诱导肺表面活性蛋白A和D （SP-A, SP-D）等集合蛋白的突变，从而使突变蛋白能够识别和中和新出现的病原体。这种机制可能会给宿主动物和人类带来进化优势。