Infection Susceptibility in Gastric Intrinsic Factor (Vitamin B ₁₂ )-Defective Mice Is Subject to Maternal Influences

Abstract

Mice harboring a mutation in the gene encoding gastric intrinsic factor (Gif), a protein essential for the absorption of vitamin B12/cobalamin (Cbl), have potential as a model to explore the role of vitamins in infection. The levels of Cbl in the blood of Giftm1a/tm1a mutant mice were influenced by the maternal genotype, with offspring born to heterozygous (high Cbl, F1) mothers exhibiting a significantly higher serum Cbl level than those born to homozygous (low Cbl, F2) equivalents. Low Cbl levels correlated with susceptibility to an infectious challenge with Salmonella enterica serovar Typhimurium or Citrobacter rodentium, and this susceptibility phenotype was moderated by Cbl administration. Transcriptional and metabolic profiling revealed that Cbl deficient mice exhibited a bioenergetic shift similar to a metabolic phenomenon commonly found in cancerous cells under hypoxic conditions known as the Warburg effect, with this metabolic effect being exacerbated further by infection. Our findings demonstrate a role for Cbl in bacterial infection, with potential general relevance to dietary deficiency and infection susceptibility.

Interplay between mitochondria and diet mediates pathogen and stress resistance in Caenorhabditis elegans

“…While malnutrition is well-known to predispose animals to infection, subtle nutritional defects, and their concomitant effects on host physiology, are more difficult to detect. Interestingly, our findings may explain an intriguing finding from a recently published study [ 75 ]. Gif mutant mice, which have compromised intestinal absorption of dietary B12, showed a striking increase in sensitivity and mortality to infection with Salmonella enterica serovar Typhimurium or Citrobacter rodentium .…”

Portrait of Tissue-Specific Coexpression Networks of Noncoding RNAs (miRNA and lncRNA) and mRNAs in Normal Tissues

“…Gastric intrinsic factor (GIF) and gastrokine 2 (GKN2) encode a glycoprotein secreted by the cells of the gastric mucosa [115, 116]. GIF is necessary for the correct absorption of vitamin B12 [115].…”

To B12 or not to B12: Five questions on the role of cobalamin in host-microbial interactions

“…In this study, mice with a genetic deletion in IF production displayed worsened pathology compared to wild-type mice and increased mortality during Salmonella and C . rodentium infection [24]. These data suggest that cobalamin absorption in a host promotes proper defense against pathogenic challenge.…”