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Host-pathogen-vector interactions of R. amblyommatis for spotted fever pathogenesis

R. amblyommatis 的宿主-病原体-载体相互作用对斑疹热发病机制的影响

基本信息

批准号：
10610881
负责人：
Hwan Keun Kim
金额：
$ 19.26万
依托单位：
STATE UNIVERSITY NEW YORK STONY BROOK
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-04-15 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10610881
关键词：
Address Adult Amblyomma Ambylomma americanum American Animals Antibodies Area Arthropod Vectors Bacteremia Behavior Biology Bite Black-legged Tick Blood Circulation Blood Vessels Borrelia lonestari Bourbon virus CCL14 gene CRISPR screen Canis familiaris Cavia Characteristics Child Clinical Cutaneous Cytopathology Cytoplasm Dermacentor Diagnosis Disease Ehrlichia chaffeensis Ehrlichia ewingii Ehrlichiosis Endothelial Cells Etiology Exanthema Exhibits Fever Francisella tularensis Frequencies Gene Mutation Generations Genes Genetic Genetic study Genome Genotype Geographic Locations Geography Habitats Headache Heartland virus Hemostatic function High Prevalence Human Immune response Immunity Infection Integration Host Factors Invaded Knowledge Laboratories Life Life Cycle Stages Long Island Microarray Analysis Midgut Midwestern United States Modeling Mus Myalgia Necrosis New England Organ Ovary Pathogenesis Pathogenicity Pathology Patients Phenotype Population Prevalence Probability Public Health Reporting Resistance Rickettsia Rickettsia Infections Rickettsia parkeri Rickettsia rickettsii Rocky Mountain Spotted Fever Role Saliva Salivary Glands Sepsis Serology Sociology Southeastern United States Southern Tick Associated Rash Illness Surveys Symptoms Texas Tick-Borne Diseases Ticks Tissues Tularemia United States Universities Vascular Endothelial Cell Vasculitis Virulence Virus Diseases Work cell injury comparative environmental change epidemiology study genome-wide human pathogen insight member novel offspring pathogen spotted fever surveillance study tick bite tick saliva tissue culture transmission process vascular inflammation vector virulence gene whole genome

项目摘要

Ticks are the most important arthropod vectors capable of transmitting a diverse array of pathogens to humans. Several environmental and sociological factors have contributed to the range and population expansion of ticks, resulting in an increased number of tick-borne diseases (TBDs) in the United States. Recent tick surveillance studies have demonstrated that Amblyomma americanum (lone star tick) has rapidly expanded northward and become the dominant tick species, displacing local tick species such as Ixodes scapularis (deer tick) and Dermacentor variabilis (American dog tick) in the Northeast and Midwest, where the increased number of patients with TBDs of unknown etiology has been observed. A. americanum poses a public health threat as the tick presents non-discriminating aggressive biting behavior and serves as a vector and reservoir for diverse human pathogens, including Rickettsia amblyommatis (rickettsiosis), Ehrlichia chaffeensis and E. ewingii (human ehrlichiosis), Francisella tularensis (tularemia), Heartland virus (Heartland virus disease), Bourbon virus (Bourbon virus disease), and Borrelia lonestari (Southern tick-associated rash illnesses). R. amblyommatis, a Gram-negative pathogen that belongs to the spotted fever group of Rickettsia, has been frequently identified from A. americanum in several parts of the United States. In contrast, the current prevalence of R. rickettsii (Rocky Mountain spotted fever, RMSF) in D. variabilis is estimated to be less than 1%. The high prevalence of R. amblyommatis, combined with the aggressive biting behavior of A. americanum, enhances the probability of human infections with R. amblyommatis. Within ticks, R. amblyommatis exhibits obligatory intracellular lifecycle in multiple organ tissues such as ovaries, midgut, and salivary glands, enabling R. amblyommatis transmission to offspring and mammalian hosts. Several lines of clinical and serological evidence suggest that R. amblyommatis is the etiological agent of RMSF-like illness. Analysis of paired sera from patients diagnosed with probable RMSF revealed that some patients developed antibodies to R. amblyommatis, but not to R. rickettsii, corroborating that R. amblyommatis may cause RMSF-like illnesses in humans. Those patients with specific reactivity to R. amblyommatis presented typical clinical manifestations of a mild RMSF with fever, headache, and myalgia. However, there is a significant gap in our understanding of R. amblyommatis biology and its virulence potential to cause rickettsiosis in mammalian hosts. Based on the available evidence of 1) the invasion and expansion of A. americanum heavily infected with R. amblyommatis in the upper Midwestern and the Northeastern United States; 2) the increasing numbers of RMSF-like cases in the same areas; 3) experimental results from our laboratory for R. amblyommatis-induced cytopathology and pathogenesis, we will investigate the genetic basis of R. amblyommatis from one of the northernmost hotspots for this species, determine the virulence potential in tissue culture and animal infection models, and study the host-pathogen-vector interactions enabling R. amblyommatis rickettsiosis.

蜱是最重要的节肢动物媒介，能够将多种病原体传播给人类几个环境和社会因素促成了范围和人口蜱的扩张，导致美国蜱传疾病（TBD）数量增加。最近的蜱监测研究表明，美洲钝眼蜱（孤星星蜱）迅速向北扩张并成为主导蜱虫物种，取代了硬蜱等当地蜱虫物种肩胛蜱（鹿蜱）和可变革蜱（美国狗蜱）在东北部和中西部，其中已经观察到患有病因不明的TBD的患者数量增加。A.美洲构成了一个公共卫生威胁，因为蜱虫表现出非歧视性的攻击性叮咬行为，和多种人类病原体的储存库，包括弱视立克次体（立克次体病）、埃里希体 chaffeensis和E.埃温氏菌（人埃里希体病）、土拉热弗朗西丝菌（土拉菌病）、哈特兰病毒（哈特兰病毒病）、波旁病毒（波旁病毒病）和孤斯疏螺旋体（南方蜱相关皮疹疾病）。R.弱视是一种属于立克次体斑点热组的革兰氏阴性病原体，经常被认为是A。在美国的几个地方。相比之下，目前 R.立克次氏体（Rocky Mountain spotted fever，RMSF）在D. variabilis估计小于百分之一R. Amblyomelia，结合A.美洲，增加了人类感染R.弱视在蜱，R。弱视表现在多个器官组织如卵巢、中肠和唾液腺中的强制性细胞内生命周期， R.传播给后代和哺乳动物宿主。几条临床和血清学路线有证据表明R.弱视是RSF样疾病的病原体。配对血清分析从诊断为可能的RMSF的患者中发现，一些患者产生了R. 对R.立克次氏体，证实R.弱视可能会导致RMSF样疾病，人类对R.弱视的典型临床表现为轻度RMSF伴发热、头痛和肌痛。然而，在我们对R的理解上存在着很大的差距。在哺乳动物宿主中引起立克次体病的可能性。基于现有证据表明：1）A. americanum严重感染R.弱视在美国中西部和东北部; 2）在美国，（3）本实验室对R.弱视诱导的细胞病理学和发病机制，我们将探讨R.从最北端的一个热点地区对于该物种，确定组织培养和动物感染模型中的毒力潜力，并研究宿主-病原体-载体相互作用使R.立克次氏体病