Division of Infectious Diseases and Center for Global Health, University of Virginia, Charlottesville, Virginia 22903, USA.
J Clin Invest. 2013 Jun;123(6):2672-84. doi: 10.1172/JCI67294.
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, further 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 Il4 and Il5 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.
蓝氏贾第鞭毛虫感染在低收入国家的儿童中几乎普遍存在，与营养不良、腹泻和发育生长迟缓的三联症有关。在这些人群中，早期儿童肠道病原体暴露的混乱中，蓝氏贾第鞭毛虫与持续性腹泻、认知缺陷、发育迟缓以及营养缺乏的具体关联结果相互矛盾，使地方性儿科贾第虫病处于平衡状态。许多地方性感染似乎无症状/亚临床，这进一步增加了蓝氏贾第鞭毛虫感染与发育迟缓之间因果关系的不确定性。我们使用营养不良断奶小鼠模型中的蓝氏贾第鞭毛虫 H3 囊感染来证明持续性贾第虫病会导致上皮细胞凋亡和隐窝增生。感染与 Th2 偏向性炎症反应和生长受损有关。营养不良加重了这些生长下降的严重程度。营养不良的衰弱小鼠在感染后表现出受损的代偿反应，并且没有观察到隐窝增生，随后绒毛结构变钝。同时，严重的营养不良阻止了感染后固有层中 B220+细胞以及黏膜 Il4 和 Il5 mRNA 的增加。这些发现增加了蓝氏贾第鞭毛虫作为“发育迟缓”病原体的潜在作用的认识，并表明，同样地，营养不良的儿童可能面临更高的蓝氏贾第鞭毛虫增强的生长下降风险。
