Mechanisms of IgA - mediated immunity to Vibrio cholerae

 描述（由申请人提供）：本研究项目的长期目标是开发更有效的口服疫苗，以对抗霍乱弧菌，霍乱的病原体，一种威胁生命的霍乱疾病，仍然在发展中国家的许多地方流行。虽然有越来越多的流行病学研究证据表明，针对细菌脂多糖（LPS）的伊加抗体是对霍乱弧菌免疫的主要决定因素，但实际上对这些抗体如何影响细菌定植肠上皮的能力一无所知。该提议将检验LPS特异性伊加（和IgG）抗体与霍乱弧菌表面的结合对细菌生理学和毒力具有直接影响的假设。目的1将验证LPS特异性伊加（和IgG）抗体诱导胆总管膜电位、通透性和超微结构变化的假设。目的2将测试的假设，LPS特异性伊加（和IgG）抗体也触发细菌毒力基因表达和信号转导途径的变化。首席研究员是IgA-病原体相互作用领域的领先专家， 工作人员具有霍乱弧菌生理学和毒力方面的专业知识。

 DESCRIPTION (provided by applicant): The long-term goal of this research project is to develop more effective oral vaccines against Vibrio cholerae, the causative agent of cholera, a life threatening diarrheal disease that remains endemic in many parts of the developing world. While there is mounting evidence from epidemiological studies to suggest that IgA antibodies directed against bacterial lipopolysaccharide (LPS) are the primary determinants of immunity to V. cholerae, virtually nothing is known about how these antibodies affect the bacterium's capacity to colonize the intestinal epithelium. This proposal will test the hypothesis that the binding of LPS-specific IgA (and IgG) antibodies to the surface of V. cholerae has direct impact on bacterial physiology and virulence. Aim 1 will test the hypothesis that LPS-specific IgA (and IgG) antibodies induce changes in V. cholerae membrane potential, permeability and ultrastructure. Aim 2 will test the hypothesis that LPS-specific IgA (and IgG) antibodies also trigger changes in the bacterial virulence gene expression and signal transduction pathways. The principal investigator is a leading expert in the field of IgA-pathogen interactions, while key personnel have expertise in V. cholerae physiology and virulence.