Recognition and phagocytosis of bacteria in Drosophila

描述（由申请人提供）：在先天免疫中，病原体相关分子模式（pamp）被模式识别受体（PRRs）识别，其激活信号级联反应和效应机制，如吞噬作用，其作用是将微生物清除出宿主系统。我们对果蝇细菌的吞噬作用很感兴趣，因为我们对果蝇的细胞免疫知之甚少，它可能是第一线的免疫反应。在初步基因筛选中，我们发现了8个影响体内大肠杆菌（一种革兰氏菌）和/或金黄色葡萄球菌（一种革兰氏菌）吞噬能力的突变。本建议的具体目的是：1。阐明两种催化肽聚糖识别蛋白（PGRP-SC1a/b和PGRP-SC2）在细菌吞噬和抗菌肽（AMP）反应激活中的作用。我们的两个吞噬突变影响PGRP-SC1a/b和PGRP-SC2的表达。我们将研究这些突变体如何影响吞噬和AMP反应。2. 为了确定是否破坏革兰氏阴性菌的外膜是必要的识别和清除细菌的果蝇免疫反应。我们认为，这可能是为了允许进入细胞壁的肽聚糖，从而触发下游AMP反应。3. 研究免疫反应或吞噬作用的重要基因如何影响体内吞噬体的成熟。我们有初步的数据表明PGRP-SC2， Rab14和amp可能对吞噬体成熟很重要。通过这些实验，我们希望了解这些基因在体内对细菌的识别和吞噬中所起的作用。

DESCRIPTION (provided by applicant): In innate immunity, pathogen associated molecular patterns (PAMPs) are recognized by pattern recognition receptors (PRRs) that activate signaling cascades and effector mechanisms, like phagocytosis which act to clear the microbes out of the host's system. We are interested in the phagocytosis of bacteria in Drosophila because not much is know about cellular immunity in flies and it may be the first-line immune response. In a pilot genetic screen, we have identified 8 mutations that affect the phagocytosis of E. coli (a Gram- bacteria) and/or S. aureus (a Gram+ bacteria) in vivo. The specific aims of this proposal are: 1. To elucidate the role two catalytic peptidoglycan recognition proteins (PGRP-SC1a/b and PGRP-SC2) play in the phagocytosis of bacteria and the activation of the antimicrobial peptide (AMP) response. Two of our phagocytosis mutations affect PGRP-SC1a/b and PGRP-SC2 expression. We will examine how these mutants affect phagocytosis and AMP responses. 2. To determine if disruption of the outer membrane of Gram-negative bacteria is necessary for recognition and clearance of the bacteria by the Drosophila immune response. We believe that this may be occuring to allow access to peptidoglycan in the cell wall which can trigger the downstream AMP responses. 3. To examine how genes important for immune responses or phagocytosis affect phagosome maturation in vivo. We have preliminary data indicating that PGRP-SC2, Rab14 and AMPs may be important for phagosome maturation. With these experiments, we hope to understand the role these genes play in recognition and phagocytosis of bacteria in vivo.