The gut flora is required for the control of intestinal infection by poly(I:C) administration in neonates

Lacroix‐Lamandé, Sonia; Guesdon, William; Drouet, Françoise; Potiron, Laurent; Lantier, Louis; Laurent, Fabrice

doi:10.4161/gmic.29154

Cited by 18 publications

(9 citation statements)

References 51 publications

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“…Oral immunization with Salmonella vaccine strains has also been shown to protect against non- Salmonella bacterial infections via sustained changes in TLR expression and non-specific macrophage activation [ 75 ]. Signaling TLR3 in combination with TLR5 [ 76 , 77 ], TLR4 [ 78 ] and TLR9 [ 24 , 38 ] independently influence Cryptosporidium infection outcomes. While prior studies have focused on TLR activation immediately prior to infection, we found that even remote selective TLR activation with CpG mimicked the S .…”

Section: Discussionmentioning

confidence: 99%

Cryptosporidium Priming Is More Effective than Vaccine for Protection against Cryptosporidiosis in a Murine Protein Malnutrition Model

et al. 2016

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Cryptosporidium is a major cause of severe diarrhea, especially in malnourished children. Using a murine model of C. parvum oocyst challenge that recapitulates clinical features of severe cryptosporidiosis during malnutrition, we interrogated the effect of protein malnutrition (PM) on primary and secondary responses to C. parvum challenge, and tested the differential ability of mucosal priming strategies to overcome the PM-induced susceptibility. We determined that while PM fundamentally alters systemic and mucosal primary immune responses to Cryptosporidium, priming with C. parvum (106 oocysts) provides robust protective immunity against re-challenge despite ongoing PM. C. parvum priming restores mucosal Th1-type effectors (CD3+CD8+CD103+ T-cells) and cytokines (IFNγ, and IL12p40) that otherwise decrease with ongoing PM. Vaccination strategies with Cryptosporidium antigens expressed in the S. Typhi vector 908htr, however, do not enhance Th1-type responses to C. parvum challenge during PM, even though vaccination strongly boosts immunity in challenged fully nourished hosts. Remote non-specific exposures to the attenuated S. Typhi vector alone or the TLR9 agonist CpG ODN-1668 can partially attenuate C. parvum severity during PM, but neither as effectively as viable C. parvum priming. We conclude that although PM interferes with basal and vaccine-boosted immune responses to C. parvum, sustained reductions in disease severity are possible through mucosal activators of host defenses, and specifically C. parvum priming can elicit impressively robust Th1-type protective immunity despite ongoing protein malnutrition. These findings add insight into potential correlates of Cryptosporidium immunity and future vaccine strategies in malnourished children.

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Section: Discussionmentioning

confidence: 99%

Cryptosporidium Priming Is More Effective than Vaccine for Protection against Cryptosporidiosis in a Murine Protein Malnutrition Model

et al. 2016

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“…Those authors also showed that resistance of mice to C. parvum could be increased by transferring intestinal mucosa from resistant animals to susceptible infant mice (7). A protective role of the gut microbiota against cryptosporidiosis was also observed in neonatal mice (8,9). That research found that the gut microbiota synergized with poly(I•C) to elicit protective intestinal immunity against C. parvum.…”

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confidence: 91%

Probiotic Product Enhances Susceptibility of Mice to Cryptosporidiosis

Oliveira

Widmer

2018

Appl Environ Microbiol

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Cryptosporidiosis, a leading cause of diarrhea among infants, is caused by apicomplexan parasites classified in the genus The lack of effective drugs is motivating research to develop alternative treatments. With this aim, the impact of probiotics on the course of cryptosporidiosis was investigated. The native intestinal microbiota of specific pathogen-free immunosuppressed mice was initially depleted with orally administered antibiotics. A commercially available probiotic product intended for human consumption was subsequently added to the drinking water. Mice were infected with oocysts. On average, mice treated with the probiotic product developed more severe infections. The probiotics significantly altered the fecal microbiota, but no direct association between ingestion of probiotic bacteria and their abundance in fecal microbiota was observed. These results suggest that probiotics indirectly altered the intestinal microenvironment or the intestinal epithelium in a way that favored proliferation of The results of our study show that responded to changes in the intestinal microenvironment induced by a nutritional supplement. This outcome paves the way for research to identify nutritional interventions aimed at limiting the impact of cryptosporidiosis.

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“…Various Cryptosporidium species are recognized weeks [17,18]. A protective role of the gut microbiota against cryptosporidiosis was also observed in neonatal mice [19,20] A protein-deficient diet was also found to increase susceptibility of mice to C. parvum [21]. This phenotype was attributed to a reduced epithelial cell turnover.…”

Section: Introductionmentioning

confidence: 97%

Deprivation of dietary fiber enhances susceptibility of mice to cryptosporidiosis

Oliveira

Bresciani

Widmer

2019

Preprint

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Based on our initial observations showing that mice consuming a probiotic product develop more severe cryptosporidiosis, we investigated the impact of other dietary interventions on the intracellular proliferation of Cryptosporidium parvum and C. tyzzeri in the mouse. Mice were orally infected with oocysts and parasite multiplication measured by quantifying fecal oocyst output. High-15 throughput sequencing of 16S ribosomal RNA amplicons was used to correlate oocyst output with diet and with the composition of the intestinal microbiota. On average, mice fed a diet without fiber (cellulose, pectin and inulin) developed more severe infections. As expected, a diet without fibers also significantly altered the fecal microbiota. Consistent with these observations, mice fed a prebiotic product sold for human consumption excreted significantly fewer oocysts. The fecal microbiota of mice 20 consuming no plant polysaccharides was characterized by a lower relative abundance of Bacteroidetes bacteria. Since bacterial metabolites play an important role in the physiology of intestinal enterocytes, we hypothesize based on these observations that the impact of diet on parasite proliferation is mediated primarily by the metabolic activity of the anaerobic microbiota, specifically by the effect of certain metabolites on the host. This model is consistent with the metabolic dependence of intracellular stages 25 of the parasite on the host cell. These observations underscore the potential of dietary interventions to alleviate the impact of cryptosporidiosis, particularly in infants at risk of recurrent enteric infections. AUTHOR SUMMARY 30The infection with Cryptosporidium parasite, a condition known as cryptosporidiosis, is a common cause of infant diarrhea in developing countries. We have previously shown that mice infected with C. parvum, one of the main cause of human cryptosporidiosis, develop a more severe infection if given probiotics. To investigate the mechanism of this effect, we fed mice prebiotics and diet lacking plant fiber. We found that fermentable fiber, whether administered as a prebiotic supplement or is part of the 35 diet, has a protective effect against cryptosporidiosis in mice. We also observed a significant association between the severity of infection and the composition of the gut microbiota. A significant inverse correlation was found between severity of cryptosporidiosis and the ratio between the abundance of bacteria belonging to the phylum Bacteroidetes and the abundance of Firmicute bacteria.This ratio is frequently viewed as a marker of a healthy microbiota. These results raise the possibility 40 that dietary interventions could be used to alleviate the impact of cryptosporidiosis. 45 as opportunistic pathogens in patients with AIDS, where cryptosporidiosis can lead to protracted diarrhea and wasting. Although immunocompetent patients heal spontaneously within a few weeks, recent studies in developing nations have pointed to Cryptosporidium as the second leading cause of infant diarrhea [2, 3]. The ...

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The gut flora is required for the control of intestinal infection by poly(I:C) administration in neonates

Cited by 18 publications

References 51 publications

Cryptosporidium Priming Is More Effective than Vaccine for Protection against Cryptosporidiosis in a Murine Protein Malnutrition Model

Cryptosporidium Priming Is More Effective than Vaccine for Protection against Cryptosporidiosis in a Murine Protein Malnutrition Model

Probiotic Product Enhances Susceptibility of Mice to Cryptosporidiosis

Deprivation of dietary fiber enhances susceptibility of mice to cryptosporidiosis

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