Persistent G. lamblia impairs growth in a murine malnutrition model
Persistent G. lamblia impairs growth in a murine malnutrition model
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DOI：
10.1172/jci67294
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发表时间：
2013-06-01
影响因子：
15.9
通讯作者：
Guerrant, Richard
中科院分区：
文献类型：
--
作者：
Bartelt, Luther A.;Roche, James;Guerrant, Richard
蓝氏贾第鞭毛虫感染在低收入国家的儿童中几乎是普遍的，并且与营养不良、腹泻和发育迟缓的三重疾病一起流行。在这些人群中，在早期儿童肠道病原体暴露的困境中，G。蓝氏贾第虫病与持续性腹泻、认知缺陷、发育迟缓和营养缺乏的特异性关联已经证明了相互矛盾的结果，使地方性小儿贾第虫病处于平衡状态。地方性环境中的许多感染似乎是无症状/亚临床的，进一步导致G.兰氏杆菌感染和发育迟缓。我们使用G。在营养不良的断奶小鼠模型中的Lamblia H3包囊感染，以证明持续性贾第虫病导致上皮细胞凋亡和隐窝增生。感染与Th 2偏向性炎症反应和生长受损相关。营养不良加重了这些生长衰退的严重性。步履蹒跚的营养不良小鼠在感染后表现出代偿反应受损，并表现出缺乏腺窝增生，随后绒毛结构变钝。同时，严重营养不良阻止了固有层中B220（+）细胞以及粘膜114和115 mRNA对感染的反应。这些发现增加了对G. Lamblia作为一种“发育不良”病原体，并表明，同样，营养不良的儿童可能在G。Lamblia增强的生长递减。
Giardia lamblia infections are nearly universal among children in low-income countries and are syndemic with the triumvirate of malnutrition, diarrhea, and developmental growth delays. Amidst the morass of early childhood enteropathogen exposures in these populations, G. lamblia-specific associations with persistent diarrhea, cognitive deficits, stunting, and nutrient deficiencies have demonstrated conflicting results, placing endemic pediatric giardiasis in a state of equipoise. Many infections in endemic settings appear to be asymptomatic/subclinical, farther contributing to uncertainty regarding a causal link between G. lamblia infection and developmental delay. We used G. lamblia H3 cyst infection in a weaned mouse model of malnutrition to demonstrate that persistent giardiasis leads to epithelial cell apoptosis and crypt hyperplasia. Infection was associated with a Th2-biased inflammatory response and impaired growth. Malnutrition accentuated the severity of these growth decrements. Faltering malnourished mice exhibited impaired compensatory responses following infection and demonstrated an absence of crypt hyperplasia and subsequently blunted villus architecture. Concomitantly, severe malnutrition prevented increases in B220(+) cells in the lamina propria as well as mucosal 114 and 115 mRNA in response to infection. These findings add insight into the potential role of G. lamblia as a "stunting" pathogen and suggest that, similarly, malnourished children may be at increased risk of G. lamblia-potentiated growth decrements.