Defensins play a crucial role in protecting mice against oral Shigella flexneri infection

Shim, Doo-Hee; Ryu, Sangryeol; Kweon, Mi‐Na

doi:10.1016/j.bbrc.2010.09.100

Cited by 21 publications

(18 citation statements)

References 33 publications

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“…Studies of MMP7(Ϫ/Ϫ) mouse susceptibility to oral infection have focused on E. coli and S. enterica serovar Typhimurium infections of the small intestine and cecum and detected reduced bacterial clearance from distal small intestine (20). In MMP7(Ϫ/Ϫ) mice infected with Shigella flexneri, increased numbers of S. flexneri were detected in colons of newborn MMP7(Ϫ/Ϫ) mice, but factors other than MMP7 deficiency or low ␣-defensin levels also may contribute to Shigella survival when Paneth cell numbers are low as they are in newborn mice (42). Because the colonic microbial burden is several orders of magnitude greater than that of the small bowel and wild type and MMP7(Ϫ/Ϫ) colonic ␣-defensins are less abundant than in wild type small intestine, ␣-defensins may affect the colonic microbiota by means other than direct peptide-mediated cell killing.…”

Section: Discussionmentioning

confidence: 99%

Alternative Luminal Activation Mechanisms for Paneth Cell α-Defensins

Mastroianni

Costales

Zaksheske

et al. 2012

Journal of Biological Chemistry

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Background: Matrix metalloproteinase-7 (MMP7) processes mouse pro-␣-defensins to bactericidal forms in Paneth cells, and MMP7(Ϫ/Ϫ) mice are considered to be ␣-defensin-null. Results: Activated ␣-defensins occur in the colonic lumen of MMP7(Ϫ/Ϫ) mice. Conclusion: ␣-Defensins are activated in MMP7(Ϫ/Ϫ) large bowel lumen by alternative proteolytic conversion mechanisms. Significance: MMP7(Ϫ/Ϫ) mice are unsuitable for studying ␣-defensin deficiency in large intestine.

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Section: Discussionmentioning

confidence: 99%

Alternative Luminal Activation Mechanisms for Paneth Cell α-Defensins

Mastroianni

Costales

Zaksheske

et al. 2012

Journal of Biological Chemistry

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“…For example, newborns are highly susceptible to Shigella flexneri , the causative agent of human bacillary dysentery, due to the lack of Paneth cells during early postnatal development. Also, MMP7-deficient mice show an increased inflammation and higher bacterial load after oral infection compared to wild type [127]. Similarly, the susceptibility to rotavirus is restricted to children under the age of 6 in human and is highest in between day 3 and 11 in mice.…”

Section: Neonatal Innate Immune Response Infections and Sepsismentioning

confidence: 99%

Neonatal Immune Adaptation of the Gut and Its Role during Infections

Tourneur

Chassin

2013

Clinical and Developmental Immunology

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The intestinal tract is engaged in a relationship with a dense and complex microbial ecosystem, the microbiota. The establishment of this symbiosis is essential for host physiology, metabolism, and immune homeostasis. Because newborns are essentially sterile, the first exposure to microorganisms and environmental endotoxins during the neonatal period is followed by a crucial sequence of active events leading to immune tolerance and homeostasis. Contact with potent immunostimulatory molecules starts immediately at birth, and the discrimination between commensal bacteria and invading pathogens is essential to avoid an inappropriate immune stimulation and/or host infection. The dysregulation of these tight interactions between host and microbiota can be responsible for important health disorders, including inflammation and sepsis. This review summarizes the molecular events leading to the establishment of postnatal immune tolerance and how pathogens can avoid host immunity and induce neonatal infections and sepsis.

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“…Because of the many similarities in immunity in early life between mice and humans (1, 2), neonatal mice provide a reasonably faithful and experimentally convenient model system for studying infection with bacterial enteropathogens. Indeed, as in humans, mouse neonates are very sensitive to oral infection with a number of bacterial enteropathogens, including Salmonella typhimurium (3, 4), Helicobacter pylori (5–7), Shigella flexneri (8–10), Vibrio cholera (11, 12), and the Enteropathogenic E. coli -related Citrobacter rodentium (13–16). Often, these susceptibilities are linked to quantitative or qualitative differences in neonatal and adult responses involving both the innate and adaptive gastrointestinal immune systems.…”

Section: Introductionmentioning

confidence: 99%

Rapid CD8+ Function Is Critical for Protection of Neonatal Mice from an Extracellular Bacterial Enteropathogen

Siefker

Adkins

2017

Front. Pediatr.

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Both human and murine neonates are characteristically highly susceptible to bacterial infections. However, we recently discovered that neonatal mice are surprisingly highly resistant to oral infection with Yersinia enterocolitica. This resistance was linked with activation of both innate and adaptive responses, involving innate phagocytes, CD4+ cells, and B cells. We have now extended these studies and found that CD8+ cells also contribute importantly to neonatal protection from Y. enterocolitica. Strikingly, neonatal CD8+ cells in the mesenteric lymph nodes (MLN) are rapidly mobilized, increasing in proportion, number, and IFNγ production as early as 48 h post infection. This early activation appears to be critical for protection since B2m−/− neonates are significantly more susceptible than wt neonates to primary Y. enterocolitica infection. In the absence of CD8+ cells, Y. enterocolitica rapidly disseminated to peripheral tissues. Within 48 h of infection, both the spleens and livers of B2m−/−, but not wt, neonates became heavily colonized, likely leading to their deaths from sepsis. In contrast to primary infection, CD8+ cells were dispensable for the generation of immunological memory protective against secondary infection. These results indicate that CD8+ cells in the neonatal MLN contribute importantly to protection against an extracellular bacterial enteropathogen but, notably, they appear to act during the early innate phase of the immune response.

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Defensins play a crucial role in protecting mice against oral Shigella flexneri infection

Cited by 21 publications

References 33 publications

Alternative Luminal Activation Mechanisms for Paneth Cell α-Defensins

Alternative Luminal Activation Mechanisms for Paneth Cell α-Defensins

Neonatal Immune Adaptation of the Gut and Its Role during Infections

Rapid CD8+ Function Is Critical for Protection of Neonatal Mice from an Extracellular Bacterial Enteropathogen

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