2011
DOI: 10.1645/ge-2848.1
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Cryptosporidium-Malnutrition Interactions: Mucosal Disruption, Cytokines, and TLR Signaling In A Weaned Murine Model

Abstract: Cryptosporidiosis is a leading cause of persistent diarrhea in children in impoverished and developing countries and has both a short- and long-term impact on the growth and development of affected children. An animal model of cryptosporidial infection that mirrors closely the complex interaction between nutritional status and infection in children, particularly in vulnerable settings such as post-weaning and malnourishment, is needed to permit exploration of the pathogenic mechanisms involved. Weaned C57BL/6 … Show more

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Cited by 64 publications
(76 citation statements)
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“…Although growth failure was present in nourished mice, the effect was modest and delayed relative to the more profound decrement seen in the setting of malnutrition. Counter to other enteric infections in malnutrition (32)(33)(34), this compounded effect cannot be explained by a higher burden of infection in the malnourished mice. Intriguingly, another investigation also demonstrated a relatively decreased burden of G. lamblia trophozoites in the small bowel following severe PD in mice (44).…”
Section: Discussionmentioning
confidence: 94%
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“…Although growth failure was present in nourished mice, the effect was modest and delayed relative to the more profound decrement seen in the setting of malnutrition. Counter to other enteric infections in malnutrition (32)(33)(34), this compounded effect cannot be explained by a higher burden of infection in the malnourished mice. Intriguingly, another investigation also demonstrated a relatively decreased burden of G. lamblia trophozoites in the small bowel following severe PD in mice (44).…”
Section: Discussionmentioning
confidence: 94%
“…We hypothesized that malnourished, weaned C57BL/6 mice would also have impaired clearance due to malnutrition-related immunosuppression. To test this hypothesis, we malnourished mice using an LP deprivation diet (2% protein), similar to our previously published protocols for Cryptosporidium infections (33,34). We infected 3-week-old mice after 8 days of LP preconditioning with 1 × 10 7 WB axenic trophozoites (assemblage A by Tpi sequencing, data not shown), 1 × 10 6 G. lamblia H3 cysts (assemblage B by Tpi sequencing, data not shown), or PBS challenge as a control.…”
Section: In Vivo Model Of Persistent G Lamblia Demonstrates Impairedmentioning
confidence: 99%
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“…In vitro and animal studies suggest a role between infection and inflammation causing deranged immune signaling leading to enteropathy and poor growth [17][18][19]. These models, which need further validation in human studies, demonstrate that specific nutrient deprivation has a profound impact on the character and intensity of inflammation [19,20], such as an apparent bias away from Th1-type primary immune responses (Bartelt, unpublished) similar to what has been shown in malnourished children in Haiti with cryptosporidiosis [21].…”
Section: Introductionmentioning
confidence: 89%
“…In vitro and animal studies suggest a role between infection and inflammation causing deranged immune signaling leading to enteropathy and poor growth [17][18][19]. These models, which need further validation in human studies, demonstrate that specific nutrient deprivation has a profound impact on the character and intensity of inflammation [19,20], such as an apparent bias away from Th1-type primary immune responses (Bartelt, unpublished) similar to what has been shown in malnourished children in Haiti with cryptosporidiosis [21]. Also, the field observation that the APOE4/4 allelotype was protective against early childhood diarrhea and the cognitive impacts in malnourished children [22] was also shown to protect malnourished transgenic mice from weight loss and parasite burden following Cryptosporidium parvum challenge [23].…”
Section: Introductionmentioning
confidence: 99%