Cryptosporidium infection causes undernutrition and, conversely, weanling undernutrition intensifies infection.

Cryptosporidium infection causes undernutrition and, conversely, weanling undernutrition intensifies infection.
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DOI:
10.1645/ge-1411.1
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发表时间:
2008-12
期刊:
The Journal of parasitology
影响因子:
--
通讯作者:
Guerrant RL
Guerrant RL
中科院分区:
其他
文献类型:
--
作者:
Coutinho BP;Oriá RB;Vieira CM;Sevilleja JE;Warren CA;Maciel JG;Thompson MR;Pinkerton RC;Lima AA;Guerrant RL

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小隐孢子虫是发展中国家儿童的主要病原体。为了研究出生后早期营养不良是否会导致更严重的微小隐球菌感染,我们评估了乳鼠生命前两周(类似于人类出生后第一年)的肠道适应和寄生虫负荷。每天将 C57BL6J 幼崽与哺乳期母鼠分离会导致营养不良。一半的幼崽每天被分开,第4天4小时,第5天8小时,第6天到第14天12小时。第6天,每只幼崽口服接种10-25μl PBS中的105至107种寄生虫。同窝对照仅接受 PBS。从第 8 天、第 11 天和第 14 天开始评估粪便的卵囊计数。在接种后第14天即感染高峰期第8天处死小鼠。获得回肠和结肠片段用于组织学、实时和逆转录酶PCR以及免疫测定。还测量了绒毛和隐窝的长度和横截面积。与未感染的对照组相比,感染 106 或 107 个卵囊的营养不良和营养不良的小鼠表现出最差的生长结果。受到营养的 106 感染小鼠的体重下降与未感染的营养不良小鼠相当。体重和绒毛还受到营养不良和隐孢子虫病的影响。在受感染的营养不良小鼠的回肠中发现了增生的隐窝和较重的炎症反应。与感染 105 或 106 个卵囊的营养不良小鼠相比,营养不良的感染小鼠表现出更大的卵囊脱落、TNF-α 和 IFN-γ 肠道水平以及 mRNA 表达。总而言之,这些研究结果表明,隐孢子虫感染可导致营养不良,相反,断奶期营养不良会加剧感染和粘膜损伤。
Cryptosporidium parvum is a leading pathogen in children in developing countries. To investigate whether early postnatal malnutrition leads to heavier C. parvum infections, we assessed intestinal adaptation and parasite load in suckling mice during the first 2 wk of life, analogous to the first postnatal yr in humans. Undernutrition was induced by daily C57BL6J pup separation from lactating dams. Half of the pups were separated daily, for 4 hr on day 4, 8 hr on day 5, and for 12 hr from day 6 until day 14. On day 6, each pup received an oral inoculum of 105 to 107 parasites in 10–25 μl of PBS. Littermate controls received PBS alone. Stools were assessed from days 8, 11, and 14 for oocyst counts. Mice were killed on day 14, 8 days postinoculation, at the peak of the infection. Ileal and colon segments were obtained for histology, real-time and reverse transcriptase PCR, and immunoassays. Villus and crypt lengths and cross-sectional areas were also measured. Undernourished and nourished mice infected with excysted 106 or 107 oocysts exhibited the poorest growth outcomes compared with their uninfected controls. Nourished 106-infected mice had comparable weight decrements to uninfected undernourished mice. Body weight and villi were additively affected by malnutrition and cryptosporidiosis. Hyperplastic crypts and heavier inflammatory responses were found in the ilea of infected malnourished mice. Undernourished infected mice exhibited greater oocyst shedding, TNF-α and IFN-γ intestinal levels, and mRNA expression compared to nourished mice infected with either 105 or 106 oocysts. Taken together, these findings show that Cryptosporidium infection can cause undernutrition and, conversely, that weanling undernutrition intensifies infection and mucosal damage.