Regulation of intestinal epithelial cell cytoskeletal remodeling by cellular immunity following gut infection

Solaymani-Mohammadi, Shahram; Singer, Steven M.

doi:10.1038/mi.2012.80

Cited by 39 publications

(38 citation statements)

References 32 publications

(57 reference statements)

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“…Conversely, in our in vivo model, crypt hyperplasia is seen following infection in nourished mice. The latter is consistent with findings that G. lamblia in immunocompetent hosts is associated with BrdU + uptake in villus epithelial cells, resulting in a relative increase in immature enterocytes at the villus base, which accounted for microvillus cytoskeletal abnormalities and disaccharidase deficiency (52). The cellular and molecular signals promoting epithelial cell proliferation in giardiasis are not well defined.…”

Section: Discussionsupporting

confidence: 82%

Persistent G. lamblia impairs growth in a murine malnutrition model

Bartelt¹,

Roche²,

Kolling³

et al. 2013

J. Clin. Invest.

120

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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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Section: Discussionsupporting

confidence: 82%

Persistent G. lamblia impairs growth in a murine malnutrition model

Bartelt¹,

Roche²,

Kolling³

et al. 2013

J. Clin. Invest.

120

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“…To quantify how Giardia infection alters the diversity and abundance of host-associated gut microbiota, we compared the gut microbiota of mice infected with Giardia to the microbiota of uninfected mice gavaged with a saline vehicle control (see Materials and Methods). Antibiotic treatment is generally required for robust experimental Giardia infections in mice (24,44). To investigate potential colonization resistance, we compared infections and commensal diversity in both antibiotic-naive and antibiotic-treated animals.…”

Section: Resultsmentioning

confidence: 99%

“…We recently reported that antibiotic treatment of mice reduced the activation of CD8 ϩ T cells in the intestinal lamina propria and intraepithelial lymphocytes expressing the ␥␦ T cell receptor (97). CD8 ϩ T cells have previously been shown to mediate microvillous shortening and reduce levels of disaccharidase activity in the small intestine (44,98). Indeed, antibiotic treatment blunted the sucrose deficiency normally seen in the GS model of infection.…”

Section: Figmentioning

confidence: 99%

Giardia Alters Commensal Microbial Diversity throughout the Murine Gut

et al. 2017

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Giardia lamblia is the most frequently identified protozoan cause of intestinal infection. Over 200 million people are estimated to have acute or chronic giardiasis, with infection rates approaching 90% in areas where Giardia is endemic. Despite its significance in global health, the mechanisms of pathogenesis associated with giardiasis remain unclear, as the parasite neither produces a known toxin nor induces a robust inflammatory response. Giardia colonization and proliferation in the small intestine of the host may, however, disrupt the ecological homeostasis of gastrointestinal commensal microbes and contribute to diarrheal disease associated with giardiasis. To evaluate the impact of Giardia infection on the host microbiota, we used culture-independent methods to quantify shifts in the diversity of commensal microbes throughout the gastrointestinal tract in mice infected with Giardia. We discovered that Giardia's colonization of the small intestine causes a systemic dysbiosis of aerobic and anaerobic commensal bacteria. Specifically, Giardia colonization is typified by both expansions in aerobic Proteobacteria and decreases in anaerobic Firmicutes and Melainabacteria in the murine foregut and hindgut. Based on these shifts, we created a quantitative index of murine Giardia-induced microbial dysbiosis. This index increased at all gut regions during the duration of infection, including both the proximal small intestine and the colon. Giardiasis could be an ecological disease, and the observed dysbiosis may be mediated directly via the parasite's unique anaerobic fermentative metabolism or indirectly via parasite induction of gut inflammation. This systemic alteration of murine gut commensal diversity may be the cause or the consequence of inflammatory and metabolic changes throughout the gut. Shifts in the commensal microbiota may explain observed variations in giardiasis between hosts with respect to host pathology, degree of parasite colonization, infection initiation, and eventual clearance.KEYWORDS Giardia, microbiome, parasite, pathogenesis G iardia lamblia is a microaerophilic protozoan parasite of humans and animals that causes significant morbidity and diarrheal disease worldwide (1, 2). Giardiasis is a zoonotic disease with diverse animal reservoirs. Parasites infect and complete their life cycle in mammalian hosts, and infected animals shed Giardia cysts into water supplies. Over 200 million people are estimated to have acute or chronic giardiasis, and rates of giardiasis approach 90% in areas where it is endemic (3, 4). When prevalent, giardiasis has been implicated as a primary cause of growth restriction for children, resulting in long-term consequences, such as stunting, failure to thrive, malnutrition, and cognitive disabilities (1, 2, 5). In addition, Giardia has been associated with substantial postclearance irritable bowel symptoms in both children and adults (1, 6-8). The significant and adverse impact of giardiasis on global human health contrasts with a considerable lack of resea...

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“…Several studies have investigated the propensity of genetically-diverse Giardia isolates to induce symptomatic disease in immunocompetent controls; it has been suggested that some given assemblages/genotypes are associated with symptomatic disease, whereas others are not (Babaei et al, 2016; Solaymani-Mohammadi and Singer, 2011; Solaymani-Mohammadi and Singer, 2013). These studies have reported conflicting results as to the association of a given assemblage/genotype of G. duodenalis and symptomatic disease and while some studies have found a correlation between G. duodenalis assemblage B and HIV infection (Matey et al, 2016), others have found no such a link (Escobedo et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Stool antigen immunodetection for diagnosis of Giardia duodenalis infection in human subjects with HIV and cancer

Nooshadokht

Kalantari-Khandani

Sharifi

et al. 2017

Journal of Microbiological Methods

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Human infection with the protozoan parasite Giardia duodenalis is one the most common parasitic diseases worldwide. Higher incidence rates of giardiasis have been reported from human subjects with multiple debilitating chronic conditions, including hypogammaglobulinemia and common variable immunodeficiency (CVID). In the current study, stool specimens were collected from 199 individuals diagnosed with HIV or cancer and immunocompetent subjects. The sensitivity of microscopy-based detection on fresh stool preparations, trichrome staining and stool antigen immunodetection for the diagnosis of G. duodenalis were 36%, 45.5% and 100%, respectively when compared with a highly sensitive stool-based PCR method as the gold standard. Further multilocus molecular analyses using glutamate dehydrogenase (gdh) and triose phosphate isomerase (tpi) demonstrated that the AI genotype of G. duodenalis was the most prevalent, followed by the AII genotype and mixed (AI+B) infections. We concluded that stool antigen immunodetection-based immunoassays and stool-based PCR amplification had comparable sensitivity and specificity for the diagnosis of G. duodenalis infections in these populations. Stool antigen detection-based diagnostic modalities are rapid and accurate and may offer alternatives to conventional microscopy and PCR-based diagnostic methods for the diagnosis of G. duodenalis in human subjects living with HIV or cancer.

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Regulation of intestinal epithelial cell cytoskeletal remodeling by cellular immunity following gut infection

Cited by 39 publications

References 32 publications

Persistent G. lamblia impairs growth in a murine malnutrition model

Persistent G. lamblia impairs growth in a murine malnutrition model

Giardia Alters Commensal Microbial Diversity throughout the Murine Gut

Stool antigen immunodetection for diagnosis of Giardia duodenalis infection in human subjects with HIV and cancer

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