关键词: Dirofilaria immitis Microfilaria Mouse model

Mesh : Animals Dogs Dirofilariasis / parasitology Mice, SCID Dirofilaria immitis Disease Models, Animal Mice Microfilariae Dog Diseases / parasitology Aedes / parasitology Larva Ivermectin / therapeutic use

来  源:   DOI:10.1038/s41598-024-63165-x   PDF(Pubmed)

Abstract:
Dirofilaria immitis is a mosquito-borne parasitic nematode that causes fatal heartworm disease in canids. The microfilariae are essential for research, including drug screening and mosquito-parasite interactions. However, no reliable methods for maintaining microfilaria long-term are currently available. Therefore, we used severe combined immunodeficiency (SCID) mice to develop a reliable method for maintaining D. immitis microfilaria. SCID mice were injected intravenously with microfilariae isolated from a D. immitis-infected dog. Microfilariae were detected in blood collected from the tail vein 218 days post-inoculation (dpi) and via cardiac puncture 296 dpi. Microfilariae maintained in and extracted from SCID mice showed infectivity and matured into third-stage larvae (L3s) in the vector mosquito Aedes aegypti. L3s can develop into the fourth stage larvae in vitro. Microfilariae from SCID mice respond normally to ivermectin in vitro. The microfilariae in SCID mice displayed periodicity in the peripheral circulation. The SCID mouse model aided in the separation of microfilariae from cryopreserved specimens. The use of SCID mice enabled the isolation and sustained cultivation of microfilariae from clinical samples. These findings highlight the usefulness of the SCID mouse model for studying D. immitis microfilaremia in canine heartworm research.
摘要:
Dirofilariaimmitis是一种蚊媒寄生线虫,可导致犬科动物致命的心丝虫病。微丝虫对研究至关重要,包括药物筛选和蚊子-寄生虫相互作用。然而,目前尚无可靠的长期维持微丝菌的方法。因此,我们使用严重联合免疫缺陷(SCID)小鼠来开发维持D.immitis微丝病的可靠方法。用从感染D.immitis的狗分离的微丝虫静脉注射SCID小鼠。在接种后218天(dpi)和通过心脏穿刺296dpi从尾静脉收集的血液中检测到微丝菌。维持在SCID小鼠中并从SCID小鼠中提取的微丝菌在媒介蚊子埃及伊蚊中表现出感染性并成熟为第三阶段幼虫(L3s)。L3s可在体外发育为第四期幼虫。SCID小鼠的微丝菌在体外对伊维菌素反应正常。SCID小鼠的微丝菌在外周循环中表现出周期性。SCID小鼠模型有助于从冷冻保存的标本中分离微丝虫。使用SCID小鼠能够从临床样品中分离和持续培养微丝虫。这些发现强调了SCID小鼠模型在研究犬心丝虫研究中的D.immitis微丝血症的有用性。
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