DEVELOPMENTAL BIOLOGY OF LEISHMANIA PROMASTIGOTES
利什曼原虫前鞭毛体的发育生物学
基本信息
- 批准号:6160570
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:
- 资助国家:美国
- 起止时间:至
- 项目状态:未结题
- 来源:
- 关键词:
项目摘要
Despite its importance as the cause of a widely distributed, highly
endemic form of cutaneous Leishmaniasis in the Old World, and as an
increasingly recognized agent of visceral disease, studies on L.
tropica have been neglected because of the absence of animal models.
Metacyclic promastigotes of L. tropica were identified based on prior
observations in L. donovani and L. major that the differentiation of
promastigotes to an infective form is accompanied by structural
modifications of the surface lipophosphoglycan (LPG). An anti-LPG
monoclonal antibody (1H2A8) specific for L. tropica was used to
negatively select for metacyclic forms in stationary cultures, and the
exceptional virulence of the purified metacyclics was verified by their
infectivity for mouse macrophages in vitro, and by their ability to
produce cutaneous lesions in foot pads of BALB/c mice, and visceral
disease in hamsters. The major finding from these preliminary animal
studies is that both cutaneous and visceral clinical isolates of L.
tropica produce similar cutaneous disease in BALB/c mice, but that the
visceral isolates were much better able to disseminate to liver and
spleen in the hamster model, suggesting that parasite intrinsic factors
determine, at least in part, clinical outcome.
We have initiated the first systematic study of the factors influencing
the transmission of Leishmania by bite. The factors we are currently
studying include the optimal time after the primary infective feed that
the flies will refeed and egest an infectious inoculum, and whether
prior sensitization of the host to sand fly saliva potentiates
transmission. Preliminary studies clearly indicate that in mice
previously bitten by uninfected sand flies, their subsequent exposure
to saliva leads to a large influx of neutrophils, macrophages and
dendritic cells into the dermis. The salivary molecules responsible for
this inflammatory response, as well as the differences in the
inflammatory response elicited by salivary components from different
sand fly species, are currently being explored.
Identifying the sand fly midgut receptor involved in promastigote
adhesion using a ligand blotting technique and affinity purification
have not been successful. We are attempting to clone the receptor by
over-expression in mammalian cell lines. A cDNA library from unfed sand
fly midgut was produced by PCR amplification of polyA+RNA using
CapSwitch oligo and 3' CDS primers. Amplified material was size
fractionated, pooled and cloned in a mammalian expression vector
containing CMV promoter and SV40 sequence. CHO transfectants will be
screened for LPG binding by flow cytometry.
尽管其重要性作为一个广泛分布,高度
项目成果
期刊论文数量(0)
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沉积物微生物燃料电池抑制Psychodidae发生机制的阐明
- 批准号:
19K04672 - 财政年份:2019
- 资助金额:
-- - 项目类别:
Grant-in-Aid for Scientific Research (C)