PUBLICATION

Intestinal alkaline phosphatase deficiency leads to lipopolysaccharide desensitization and faster weight gain

Authors
Yang, Y., Millán, J.L., Mecsas, J., Guillemin, K.
ID
ZDB-PUB-141029-4
Date
2015
Source
Infection and Immunity   83(1): 247-58 (Journal)
Registered Authors
Guillemin, Karen
Keywords
none
MeSH Terms
  • Alkaline Phosphatase/deficiency*
  • Animals
  • Female
  • Gram-Negative Bacteria/immunology*
  • Immune Tolerance*
  • Intestines/enzymology*
  • Intestines/microbiology*
  • Lipopolysaccharides/immunology*
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Weight Gain
PubMed
25348635 Full text @ Infect. Immun.
Abstract
Animals develop in the presence of complex microbial communities and early host responses to these microbes can influence key aspects of development, such as maturation of the immune system, in ways that impact adult physiology. We previously showed that the zebrafish intestinal alkaline phosphatase (ALPI) gene alpi.1 was induced by Gram-negative bacteria-derived lipopolysaccharide (LPS), a process dependent on myeloid differentiation primary response gene (88) (MYD88), and functioned to detoxify LPS and prevent excessive host inflammatory responses to commensal microbiota in the newly colonized intestine. In the present study, we examined whether the regulation and function of ALPI were conserved in mammals. We found that among the mouse ALPI genes, Akp3 was specifically upregulated by the microbiota, but through a mechanism independent of LPS or MYD88. We showed that disruption of Akp3 did not significantly affect intestinal inflammatory responses to commensal microbiota or animal susceptibility to Yersinia pseudotuberculosis infection. However, we found that Akp3(-/-) mice acquired LPS tolerance during post-weaning development, suggesting that Akp3 plays an important role in immune education. Finally, we demonstrated that inhibiting LPS sensing with a mutation in CD14 abrogated the accelerated weight gain in Akp3(-/-) mice receiving a high fat diet, suggesting that the weight gain is caused by excessive LPS in Akp3(-/-) mice.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping