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Updated: Mar 8, 2026
A Neonatal Imaging Model of Gram-Negative Bacterial Sepsis
Published on: August 12, 2020
Rapid CD8+ Function Is Critical for Protection of Neonatal Mice from an Extracellular Bacterial Enteropathogen
David T Siefker1, Becky Adkins2
1Department of Pediatrics, Le Bonheur Children's Medical Center , Memphis, TN , USA.
Insights
Neonatal mice resist oral Yersinia enterocolitica infection due to CD8+ T cells in the mesenteric lymph nodes. These cells are crucial for early protection against bacterial dissemination and sepsis.
Area of Science:
- Immunology
- Microbiology
- Neonatal Research
Background:
- Neonates exhibit high susceptibility to bacterial infections.
- Neonatal mice show unexpected resistance to oral Yersinia enterocolitica infection.
- Previous studies identified innate phagocytes, CD4+ T cells, and B cells in this resistance.
Purpose of the Study:
- To investigate the role of CD8+ T cells in neonatal protection against Yersinia enterocolitica.
- To determine the timing and mechanism of CD8+ T cell involvement.
- To assess the necessity of CD8+ T cells for immunological memory.
Main Methods:
- Oral infection of wild-type (wt) and beta-2-microglobulin-deficient (B2m-/-) neonatal mice with Yersinia enterocolitica.
- Analysis of CD8+ T cell populations, proportion, and IFNγ production in mesenteric lymph nodes (MLN) at 48 hours post-infection.
- Assessment of bacterial dissemination to spleen and liver in B2m-/- versus wt neonates.
- Evaluation of protection against secondary infection in the absence of CD8+ T cells.
Main Results:
- Neonatal CD8+ T cells in MLN are rapidly mobilized, increasing in proportion, number, and IFNγ production within 48 hours of Y. enterocolitica infection.
- B2m-/- neonates, lacking functional CD8+ T cells, are significantly more susceptible to primary infection.
- Absence of CD8+ T cells leads to rapid dissemination of Y. enterocolitica to peripheral tissues (spleen, liver), resulting in sepsis and mortality.
- CD8+ T cells are dispensable for generating immunological memory against secondary Y. enterocolitica infection.
Conclusions:
- CD8+ T cells in the neonatal MLN play a critical role in early protection against oral Yersinia enterocolitica infection.
- These CD8+ T cells appear to function during the innate phase of the immune response, preventing bacterial dissemination and sepsis.
- CD8+ T cell-mediated protection is essential for primary infection but not for establishing long-term immunological memory.
Abstract:
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.
