Malaria and allergic inflammatory changes to the gut barrier
Malaria and allergic inflammatory changes to the gut barrier
批准号:
10170213
负责人:
Shirley Luckhart
金额:
$46.03万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2018
资助国家:
美国
项目状态:
已结题
起止时间:
2018-06-01 至 2024-05-31
关键词:
AcuteAddressAdultAfrica South of the SaharaAfricanAllergicAllergic inflammationAntibiotic ResistanceAntibioticsAntimalarialsAreaBacteremiaBacteriaBasophiliaBasophilsBiologyBloodBlood ProteinsBlood capillariesCase Fatality RatesCellsChildChronicChymaseClinicalCountryDataDefectEndotheliumEnterobacteriaceaeEpithelialFailureFalciparum MalariaFunctional disorderFutureHistamineHospitalizationHumanIL3 GeneIgEImmuneImmune responseImmunityImmunoglobulin Class SwitchingImmunologicsIncidenceInfectionInflammatoryInterleukin-10Interleukin-13Interleukin-15Interleukin-18Interleukin-4InterventionIntestinal permeabilityIntestinesKenyaLeadLeaky GutLinkLiteratureMalabsorption SyndromesMalariaModelingMucous MembraneMusOutcomeParasitemiaParasitesPeptide HydrolasesPermeabilityPhenotypePlasmodium yoeliiPrevalencePublishingReportingResearchResourcesRiskSepsisSeveritiesSignal TransductionTPT1 geneTestingTissuesWorkWorld Health Organizationbasecell injurycomorbiditycytokineexpectationgastrointestinalgut bacteriainsightintestinal barriermalaria infectionmast cellmastocytosismicrobialmortalitynovelrecruittransmission process
中文摘要
项目总结/文摘
英文摘要
PROJECT SUMMARY/ABSTRACT
Bacteremia associated with malaria is a significant cause of mortality among children in sub-Saharan Africa
and is also prevalent in adults in some malarious regions. Bacteremic children and adults are difficult to identify
and many have blood infections with isolates that are multi-antibiotic-resistant. The high occurrence of
bacteremia suggests that malaria induces a “leaky gut,” an intestinal barrier dysfunction that facilitates escape
of bacteria from the gut lumen into the blood with resulting serious sequelae. Recent studies have
documented allergic inflammation in malaria, but no studies to date have linked this phenomenon to increased
intestinal permeability observed in both acute and resolving clinical malaria. Our published and preliminary
studies suggest that malaria-induced innate signals, including early cytokine synthesis and basophil activation,
lead to mast cell influx into the intestine. Here, activated mast cells damage the physical barrier and suppress
host immune responses that limit spread of enteric bacteria that cross the damaged physical barrier. In these
studies, we will use our established models to examine the contributions of early innate signals and basophils
– cells for which no function in malaria has been described – in promoting mastocytosis and the leaky gut
phenotype we have observed. We will also determine to what extent malaria-induced mast cell degradation of
the physical and immunological barriers of the intestine is dependent on mast cell proteases and mast cell-
derived cytokines that are relevant to our observations. It is our expectation that our work will elucidate new
mechanisms underlying the importance of allergic inflammation to mucosal barrier degradation in malaria. The
outcome of the proposed research is likely to provide novel paradigms for future interventions to reduce the
incidence of malaria-associated bacteremia. This work is significant because it directly addresses an important
co-morbidity of malaria and will provide novel mechanistic insights into well-documented – and heretofore
unlinked – clinical observations.
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DOI:
10.3389/fphys.2022.911097
发表时间:
2022
期刊:
Frontiers in physiology
影响因子:
4
作者:
[]
通讯作者:
DOI:
10.3389/fphys.2023.1247316
发表时间:
2023
期刊:
FRONTIERS IN PHYSIOLOGY
影响因子:
4
作者:
[Coles, Taylor A. A., Briggs, Anna M. M., Hambly, Malayna G. G., Cespedes, Nora, Fellows, Abigail M. M., Kaylor, Hannah L. L., Adams, Alexandria D. D., Van Susteren, Grace, Bentil, Ronald E. E., Robert, Michael A. A., Riffell, Jeffrey A. A., Lewis, Edwin E. E., Luckhart, Shirley]
通讯作者:
Luckhart, Shirley
DOI:
10.1186/s12864-021-07698-9
发表时间:
2021-05-24
期刊:
BMC genomics
影响因子:
4.4
作者:
[Andrews KR, Hunter SS, Torrevillas BK, Céspedes N, Garrison SM, Strickland J, Wagers D, Hansten G, New DD, Fagnan MW, Luckhart S]
通讯作者:
Luckhart S
DOI:
10.3390/biom11050719
发表时间:
2021-05-11
期刊:
Biomolecules
影响因子:
5.5
作者:
[Rodriguez AM, Hambly MG, Jandu S, Simão-Gurge R, Lowder C, Lewis EE, Riffell JA, Luckhart S]
通讯作者:
Luckhart S
DOI:
10.1128/iai.00427-20
发表时间:
2020-11-16
期刊:
Infection and immunity
影响因子:
3.1
作者:
[Céspedes N, Donnelly E, Garrison S, Haapanen L, Van De Water J, Luckhart S]
通讯作者:
Luckhart S
How to starve a parasite: Manipulating CoA biosynthesis to control Plasmodium development in the mosquito
-
批准号:10656980
-
项目类别:
-
资助金额:$62.25万
-
财政年份:2023
-
负责人:Shirley Luckhart
-
依托单位:
Biogenic amines, malaria and manipulation of mosquito physiology and behavior.
-
批准号:10515589
-
项目类别:
-
资助金额:$55.68万
-
财政年份:2022
-
负责人:Shirley Luckhart
-
依托单位:
Biogenic amines, malaria and manipulation of mosquito physiology and behavior.
-
批准号:10679076
-
项目类别:
-
资助金额:$54.45万
-
财政年份:2022
-
负责人:Shirley Luckhart
-
依托单位:
Midgut mitochondrial function as a driver of resistance and fitness in mosquitoes
-
批准号:9752692
-
项目类别:
-
资助金额:$72.64万
-
财政年份:2018
-
负责人:Shirley Luckhart
-
依托单位:
Harnessing midgut mitochondrial dynamics to enhance Anopheline mosquito fitness
-
批准号:8881816
-
项目类别:
-
资助金额:$77.55万
-
财政年份:2014
-
负责人:Shirley Luckhart
-
依托单位:
Fluidigm BioMark HD MX/HX Real-Time PCR System
-
批准号:8446862
-
项目类别:
-
资助金额:$26.12万
-
财政年份:2013
-
负责人:Shirley Luckhart
-
依托单位:
The Burden of Malaria Transmission due to Asymptomatic HIV Co-Infection
-
批准号:8549951
-
项目类别:
-
资助金额:$53.39万
-
财政年份:2012
-
负责人:Shirley Luckhart
-
依托单位:
The Burden of Malaria Transmission due to Asymptomatic HIV Co-Infection
-
批准号:8711275
-
项目类别:
-
资助金额:$55.49万
-
财政年份:2012
-
负责人:Shirley Luckhart
-
依托单位:
The Burden of Malaria Transmission due to Asymptomatic HIV Co-Infection
-
批准号:8466428
-
项目类别:
-
资助金额:$57.1万
-
财政年份:2012
-
负责人:Shirley Luckhart
-
依托单位:
EFFECTS OF MALARIA ON PARASITE INFECTION ON INTESTINAL RESPONSE
-
批准号:8357364
-
项目类别:
-
资助金额:$5.04万
-
财政年份:2011
-
负责人:Shirley Luckhart
-
依托单位:
Systems biology approach to MAPK regulation of malaria infection in A. stephensi
-
批准号:7873030
-
项目类别:
-
资助金额:$66.48万
-
财政年份:2009
-
负责人:Shirley Luckhart
-
依托单位:
Systems biology approach to MAPK regulation of malaria infection in A. stephensi
-
批准号:8117371
-
项目类别:
-
资助金额:$5.4万
-
财政年份:2009
-
负责人:Shirley Luckhart
-
依托单位:
Systems biology approach to MAPK regulation of malaria infection in A. stephensi
-
批准号:8302377
-
项目类别:
-
资助金额:$69.43万
-
财政年份:2009
-
负责人:Shirley Luckhart
-
依托单位:
Systems biology approach to MAPK regulation of malaria infection in A. stephensi
-
批准号:7737237
-
项目类别:
-
资助金额:$68.14万
-
财政年份:2009
-
负责人:Shirley Luckhart
-
依托单位:
Systems biology approach to MAPK regulation of malaria infection in A. stephensi
-
批准号:8487341
-
项目类别:
-
资助金额:$60.18万
-
财政年份:2009
-
负责人:Shirley Luckhart
-
依托单位:
Systems biology approach to MAPK regulation of malaria infection in A. stephensi
-
批准号:8084146
-
项目类别:
-
资助金额:$69.81万
-
财政年份:2009
-
负责人:Shirley Luckhart
-
依托单位:
Cross-talk among mosquito and mammalian immune factors
-
批准号:6726588
-
项目类别:
-
资助金额:$12.89万
-
财政年份:2004
-
负责人:Shirley Luckhart
-
依托单位:
Cross-talk among mosquito and mammalian immune factors
-
批准号:6836534
-
项目类别:
-
资助金额:$32.09万
-
财政年份:2004
-
负责人:Shirley Luckhart
-
依托单位:
Plasmodium signaling of innate immunity in Anopheles
-
批准号:6963359
-
项目类别:
-
资助金额:$24.93万
-
财政年份:2004
-
负责人:Shirley Luckhart
-
依托单位:
Cross-talk among mosquito and mammalian immune factors
-
批准号:7162526
-
项目类别:
-
资助金额:$30.53万
-
财政年份:2004
-
负责人:Shirley Luckhart
-
依托单位:
海外基金