Amazonian Center of Excellence in Malaria Research
亚马逊疟疾研究卓越中心
基本信息
- 批准号:10441617
- 负责人:
- 金额:$ 23.19万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2010
- 资助国家:美国
- 起止时间:2010-07-01 至 2024-03-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAddressAnti-DNA AntibodiesAntibodiesAntibody FormationAntigensAreaB-Lymphocyte SubsetsB-LymphocytesBiological MarkersBiteBrazilCD8-Positive T-LymphocytesCTLA4 geneCell physiologyCellsClinicalCommunitiesCulicidaeDendritic CellsDevelopmentDiagnosisDiseaseDisease OutcomeDisease ReservoirsEpigenetic ProcessEquilibriumFeverFever ChillsGrowthHeadacheHost resistanceHumanHypersensitivityImmuneImmune responseImmunityImmunologic MarkersImmunologicsImmunologyIn VitroIndividualInfectionInflammationInflammation MediatorsInflammatoryInflammatory ResponseInnate Immune ResponseInterferon Type IIInterleukin-17Interleukin-2Interleukin-4Interleukin-5InterruptionLeadLearningLongitudinal StudiesMalariaMediatingMemoryMerozoite Surface Protein 1ModelingMonitorNatural ImmunityNucleic AcidsOutcomeParasite ControlParasitemiaParasitesPathogenesisPatientsPeruPhagocytesPlasmaPlasmodiumPlasmodium falciparumPlasmodium vivaxPlayPopulationProcessProductionRegulationRegulatory T-LymphocyteResearchResistanceRoleSamplingSideSigns and SymptomsStimulusSuperoxidesSymptomsT cell responseT-LymphocyteTNF geneTestingTimeToll-like receptorsacquired immunitybiomarker identificationcell mediated immune responsecirculating biomarkersclinical predictorscurative treatmentscytokineepidemiology studyexperimental studyhistone modificationimmunoregulationinsightmRNA Expressionmalaria infectionmalaria transmissionmicrobialmonocyteneutrophilnovel vaccinespredicting responsepredictive markerpreventprogrammed cell death protein 1prospectivereceptorrecurrent infectionresponsesystemic inflammatory responsetheoriestransmission processvector mosquito
项目摘要
PROJECT SUMMARY
Both the innate and acquired immunity play important roles on systemic inflammation and pathogenesis of
malaria as well as host resistance to Plasmodium infection. When patients are symptomatic with disease, they
generally seek curative therapy, thus interrupting potential transmission. In contrast, individuals with
asymptomatic disease, at least in theory, remain as reservoirs of disease. In this project, we will address
questions related to the innate and acquired immune responses that are relevant to understanding the
emergence and persistence of asymptomatic malaria individuals. Our previous epidemiological studies in the
Amazon suggest that multiple malaria infections result in substantial immunity, which is able to control, but not
eliminate malaria infection. In contrast to the acutely ill patients, the malaria immune individuals do not display
systemic inflammation and signs of disease. Our overall hypothesis is that innate immune cells from
individuals with low and persistent parasitemia, become hyporesponsive to Plasmodium stimulation
preventing systemic inflammation, but at the same time being unable to promote an acquired immune
response that is efficient in eliminating infection. We believe that despite the low levels of parasitemia, and
the predicted low rate of transmission per mosquito bite, such patients continue to be infective over long
periods of time and hence represent a silent barrier to efforts to eliminate malaria in the Amazon. In this
project, we propose to compare the innate and acquire immune responses elicited by Plasmodium infection in
acutely ill and asymptomatic patients, and to define mechanisms that are potentially involved in modulating the
systemic inflammation and preventing parasite elimination in asymptomatic malaria patients. Our first aim is to
compare the inflammatory response and responsiveness of innate immune cells from clinically ill and
asymptomatic malaria patients. In the second aim we will compare the development of humoral and cellular
acquired immune responses as well as immunoregulatory mechanisms that may influence hyper and hypo
innate immune responses in patients undergoing acute versus asymptomatic P. vivax or P. falciparum
infection. Finally, in Aim 3 we will investigate in longitudinal studies, various immunological, parasitological and
clinical parameters in patients with recurrent infection. We intend to validate the biomarkers defined in Aims 1
and 2, and to interrogate whether asymptomatic patients are prone to develop no diseases in recurrent
infections. We will also search for immunological correlates of infectivity of symptomatic and asymptomatic P.
vivax parasitemics for colonized An. darlingi mosquitoes. Outcomes of these experiments will identify innate
immune biomarkers as well as B and T cell responses that are predictive of disease outcome and mosquito
transmission. If successful, our studies will provide important information for monitoring silent infection in
infective asymptomatic individuals and potentially new insights to further control malaria transmission in hypo-
endemic areas.
项目总结
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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RICARDO TOSTES GAZZINELLI其他文献
RICARDO TOSTES GAZZINELLI的其他文献
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{{ truncateString('RICARDO TOSTES GAZZINELLI', 18)}}的其他基金
Granzyme and Granulysin Mediated Death of Trypanosoma cruzi
颗粒酶和颗粒溶素介导的克氏锥虫死亡
- 批准号:
9229525 - 财政年份:2016
- 资助金额:
$ 23.19万 - 项目类别:
Granzyme and Granulysin Mediated Death of Trypanosoma cruzi
颗粒酶和颗粒溶素介导的克氏锥虫死亡
- 批准号:
9104713 - 财政年份:2016
- 资助金额:
$ 23.19万 - 项目类别:
Amazonian Center of Excellence in Malaria Research
亚马逊疟疾研究卓越中心
- 批准号:
10598090 - 财政年份:2010
- 资助金额:
$ 23.19万 - 项目类别:
2009 Molecular Approaches for Emergent Re-emergent Tropical Diseases Gordon Resea
2009 年新兴热带病的分子方法 Gordon Resea
- 批准号:
7611715 - 财政年份:2009
- 资助金额:
$ 23.19万 - 项目类别:
Role of Polymorphonuclear Phagocytes in Malaria Sepsis
多形核吞噬细胞在疟疾败血症中的作用
- 批准号:
7753475 - 财政年份:2009
- 资助金额:
$ 23.19万 - 项目类别:
Role of Polymorphonuclear Phagocytes in Malaria Sepsis
多形核吞噬细胞在疟疾败血症中的作用
- 批准号:
7894695 - 财政年份:2009
- 资助金额:
$ 23.19万 - 项目类别:
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