Does <i>Giardia lamblia</i> Cause Villous Atrophy in Children?: A Retrospective Cohort Study of the Histological Abnormalities in Giardiasis

Koot, Bart; Kate, Fiebo J.W. ten; Juffrie, Mohammad; Rosalina, Ina; Taminiau, Jan J.A.M.; Benninga, Marc A.

doi:10.1097/mpg.0b013e31818de3c4

Cited by 53 publications

(30 citation statements)

References 19 publications

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“…To date, increases in CD4 ϩ T cells have been reported only in the Peyer's patches of G. muris-infected mice, and increased IEL numbers have been found in both G. duodenalis and G. muris infections (6,10,35,36). The relative abundances of T cell populations within the IEL, however, are unaltered throughout infection in our model.…”

Section: Infection With G Duodenalis Results In Increased Cd4mentioning

confidence: 50%

The Microbiota Contributes to CD8⁺T Cell Activation and Nutrient Malabsorption following Intestinal Infection with Giardia duodenalis

Keselman

Maloney

et al. 2016

Infect Immun

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Giardia duodenalis is a noninvasive luminal pathogen that impairs digestive function in its host in part by reducing intestinal disaccharidase activity. This enzyme deficiency has been shown in mice to require CD8 ؉ T cells. We recently showed that both host immune responses and parasite strain affected disaccharidase levels during murine giardiasis. However, high doses of antibiotics were used to facilitate infections in that study, and we therefore decided to systematically examine the effects of antibiotic use on pathogenesis and immune responses in the mouse model of giardiasis. We found that antibiotic treatment did not overtly increase the parasite burden but significantly limited the disaccharidase deficiency observed in infected mice. Moreover, while infected mice had more activated CD8 ؉ ␣␤ T cells in the small intestinal lamina propria, this increase was absent in antibiotictreated mice. Infection also led to increased numbers of CD4 ؉ ␣␤ T cells in the lamina propria and activation of T cell receptor ␥␦-expressing intraepithelial lymphocytes (IEL), but these changes were not affected by antibiotics. Finally, we show that activated CD8؉ T cells express gamma interferon (IFN-␥) and granzymes but that granzymes are not required for sucrase deficiency. We conclude that CD8؉ T cells become activated in giardiasis through an antibiotic-sensitive process and contribute to reduced sucrase activity. These are the first data directly demonstrating activation of CD8؉ T cells and ␥␦ T cells during Giardia infections. These data also demonstrate that disruption of the intestinal microbiota by antibiotic treatment prevents pathological CD8 ؉ T cell activation in giardiasis.T he protozoan Giardia duodenalis is a major cause of parasitic diarrheal disease worldwide. Infection with G. duodenalis provides an interesting model for studying mucosal immunity, as some of the immunopathology observed in human patients and infected animals resembles that of common noninfectious intestinal disorders. The reduction of intestinal disaccharidase enzymes, for example, is a pathological hallmark of giardiasis and is also commonly observed in gastroenteritis, celiac disease, ulcerative colitis, and Crohn's disease patients (1-4). Therefore, there are likely overlapping mechanisms involved. The reduction of disaccharidase enzymes in giardiasis results from a shortening of the intestinal epithelial microvilli structures and reflects a general impairment of digestion and nutrient absorption (5-7). We have demonstrated that wild-type mice exhibit reduced disaccharidase activity following infection with G. duodenalis but that CD4Another study has demonstrated that the adoptive transfer of purified CD8 ϩ T cells, but not CD4 ϩ T cells, from Giardia muris-infected mice into athymic naive recipients is sufficient to recapitulate shortening of microvilli and intestinal disaccharidase reduction (7). Collectively, these data suggest that CD8 ϩ T cells are involved in the pathological reduction of intestinal disaccharidases following infection...

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Section: Infection With G Duodenalis Results In Increased Cd4mentioning

confidence: 50%

The Microbiota Contributes to CD8⁺T Cell Activation and Nutrient Malabsorption following Intestinal Infection with Giardia duodenalis

Keselman

Maloney

et al. 2016

Infect Immun

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“…The immune response at these time points is characterized by a predominance of B220 + cells in the lamina propria, elevated Il4 and Il5 mRNA, and intraepithelial eosinophils, consistent with a Th2-biased response. Similarly, markers of Th2 responses have been documented in human infections, including eosinophilic infiltrates in approximately one-third of jejunal biopsies from children (40), elevated IL-4 and IL-5 in stools of children who fail to clear Giardia (41), and elevated serum IL-13 following acute infection in adults (45). The mechanisms driving this response are poorly understood, and the clinical studies did not exclude the presence of coinfecting helminths, which is associated with both mucosal eosinophils and susceptibility to G. lamblia (46).…”

Section: Discussionmentioning

confidence: 99%

“…Humans demonstrate variable immune responses to G. lamblia infections, including approximately 30% of jejunal biopsies from infected children that show increased eosinophils (40). Histopathological staining of duodenal tissues at 22 dpi in both RP-fed and LP-fed infected mice and 15 dpi in the LP-fed mice demonstrated increased intraepithelial eosinophils in crypts (mean ± SEM cells per villus-crypt unit; 7.717 ± 1.082, RP-fed G. lamblia vs. 1.550 ± 0.1384 RP-fed control mice, P < 0.001; 5.033 ± 0.6259 LP-fed G. lamblia mice 22 dpi vs. 1.500 ± 0.1571 LP-fed control mice, P < 0.001; 5.220 ± 0.7703 LP-fed G. lamblia mice 15 dpi vs. 1.500 ±.1571 LP-fed control mice, P < 0.001), and in villi (mean ± SEM cells per villus-crypt unit; 7.950 ± 1.636 RP-fed G. lamblia mice vs. 2.083 ± 0.2915 RP-fed control mice, P = 0.0054; 4.967 ± 0.8065 LP-fed G. lamblia mice 22 dpi vs. 2.600 ± 0.4450 LP-fed control mice, P = 0.0279; 4.160 ± 0.5776 LP-fed G. lamblia mice 15 dpi vs. 2.600 ± 0.4450 LP-fed control mice, P = 0.0575) compared with controls (Figure 4,…”

Section: Malnutrition Blunts Eosinophil Infiltration and Il4 And Il5 mentioning

confidence: 99%

Persistent G. lamblia impairs growth in a murine malnutrition model

Bartelt¹,

Roche²,

Kolling³

et al. 2013

J. Clin. Invest.

119

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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. lambliapotentiated growth decrements.

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“…Only monitoring the clinical progression of these patients and following them up will answer this question. Some conditions such as Giardia, cryptosporidium and isosporan infections or inflammatory bowel disease may lead to abnormalities in bowel histology such as intraepithelial infiltrate (Marsh I) or crypt hyperplasia (Marsh II) due to chronic inflammation (5,29,41) . In the present study, perhaps patient #2 could be considered to have celiac disease in view of the presence of gastrointestinal symptoms, anti-tTG positivity, a histological diagnosis of duodenal mucosa with Marsh I and HLA DQ02 positivity.…”

Section: Discussionmentioning

confidence: 99%

Prevalence of Celiac Disease in Children With Epilepsy

Vieira

Jatobá

Matos

et al. 2013

Arq. Gastroenterol.

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-Context -Neurological symptoms have been well-documented in patients with celiac disease, nevertheless, the presumption of a greater prevalence of epilepsy in celiac patients remains controversial. Objectives -To determine the frequency of celiac disease in children and adolescents with idiopathic or cryptogenic epilepsy. Methods -A cross-sectional study. One hundred pediatric patients with non-symptomatic epilepsy were followed-up at two public pediatric neurology clinics in Salvador, Bahia, Brazil. Screening for celiac disease was performed by serial measurements of IgA anti-transglutaminase and IgA anti-endomysium antibodies, followed by bowel biopsy in positive cases. HLA DQ02 and DQ08 were investigated in seropositive individuals, assessing the type of seizures, the number of antiepileptic drugs used and the presence gastrointestinal symptoms. Results -Three (3.0%) patients tested anti-tTG-positive, two with normal duodenal mucosa (Marsh 0) and one with intraepithelial infiltrate (Marsh I). No villous atrophy of the duodenal mucosa (Marsh III) celiac disease was found. Two patients tested positive for HLA DQ02; none were DQ08 positive.Conclusion -The present study failed to prove the association between celiac disease and epilepsy. HEADINGS -Celiac disease. Epilepsy. Disabled children.

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Does Giardia lamblia Cause Villous Atrophy in Children?: A Retrospective Cohort Study of the Histological Abnormalities in Giardiasis

Cited by 53 publications

References 19 publications

The Microbiota Contributes to CD8⁺T Cell Activation and Nutrient Malabsorption following Intestinal Infection with Giardia duodenalis

The Microbiota Contributes to CD8⁺T Cell Activation and Nutrient Malabsorption following Intestinal Infection with Giardia duodenalis

Persistent G. lamblia impairs growth in a murine malnutrition model

Prevalence of Celiac Disease in Children With Epilepsy

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Does Giardia lamblia Cause Villous Atrophy in Children?: A Retrospective Cohort Study of the Histological Abnormalities in Giardiasis

Cited by 53 publications

References 19 publications

The Microbiota Contributes to CD8+T Cell Activation and Nutrient Malabsorption following Intestinal Infection with Giardia duodenalis

The Microbiota Contributes to CD8+T Cell Activation and Nutrient Malabsorption following Intestinal Infection with Giardia duodenalis

Persistent G. lamblia impairs growth in a murine malnutrition model

Prevalence of Celiac Disease in Children With Epilepsy

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Product

Resources

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The Microbiota Contributes to CD8⁺T Cell Activation and Nutrient Malabsorption following Intestinal Infection with Giardia duodenalis

The Microbiota Contributes to CD8⁺T Cell Activation and Nutrient Malabsorption following Intestinal Infection with Giardia duodenalis