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Updated: Jul 4, 2025
Evaluation of Host-Pathogen Responses and Vaccine Efficacy in Mice
Published on: February 22, 2019
Age-dependent natural killer cell and interferon γ deficits contribute to severe pertussis in infant mice
Ashley E Mitchell1, Karen M Scanlon1, Emily M Flowers1
1Department of Microbiology and Immunology, University of Maryland School of Medicine, 685 W. Baltimore St., Baltimore, MD 21201, United States.
Insights
Infant susceptibility to Bordetella pertussis is linked to immature natural killer (NK) cells and low interferon gamma (IFN-γ). Restoring NK cell function or IFN-γ levels in infants reduces lethal pertussis infection.
Area of Science:
- Immunology
- Infectious Diseases
- Pediatrics
Background:
- Infants are uniquely vulnerable to certain respiratory infections like pertussis.
- Adult immunity involves natural killer (NK) cells producing interferon gamma (IFN-γ) to control Bordetella pertussis.
- Infant pertussis outcomes mirror those in NK cell- and IFN-γ-deficient adults.
Purpose of the Study:
- To investigate age-dependent differences in NK cell function and IFN-γ production during Bordetella pertussis infection.
- To determine if NK cell deficits contribute to severe infant pertussis.
Main Methods:
- Comparison of Bordetella pertussis infection in infant and adult mouse models.
- Analysis of NK cell frequency, maturation, and cytokine profiles (IFN-γ, IL-12p70).
- Adoptive transfer of adult NK cells and administration of exogenous IFN-γ.
Main Results:
- Infant mice showed impaired IFN-γ upregulation and significant bacterial dissemination.
- Fewer pulmonary NK cells were observed in infected infant mice compared to adults.
- Infant NK cells exhibited an immature phenotype, with no IL-12p70 induction.
Conclusions:
- Age-associated deficits in NK cell-derived IFN-γ are a key factor in severe infant pertussis.
- This mechanism may underlie susceptibility to other pathogens in infants.
- Therapeutic strategies targeting NK cells or IFN-γ could be beneficial for infant respiratory infections.
Abstract:
Many respiratory infections are selectively injurious to infants, yet the etiology of age-associated susceptibility is unknown. One such bacterial pathogen is Bordetella pertussis. In adult mice, innate interferon γ (IFN-γ) is produced by natural killer (NK) cells and restricts infection to the respiratory tract. In contrast, infant pertussis resembles disease in NK cell- and IFN-γ-deficient adult mice that experience disseminated lethal infection. We hypothesized that infants exhibit age-associated deficits in NK cell frequency, maturation, and responsiveness to B. pertussis, associated with low IFN-γ levels. To delineate mechanisms behind age-dependent susceptibility, we compared infant and adult mouse models of infection. Infection in infant mice resulted in impaired upregulation of IFN-γ and substantial bacterial dissemination. B. pertussis-infected infant mice displayed fewer pulmonary NK cells than adult mice. Furthermore, the NK cells in the infant mouse lungs had an immature phenotype, and the infant lung showed no upregulation of the IFN-γ-inducing cytokine IL-12p70. Adoptive transfer of adult NK cells into infants, or treatment with exogenous IFN-γ, significantly reduced bacterial dissemination. These data indicate that the lack of NK cell-produced IFN-γ significantly contributes to infant fulminant pertussis and could be the basis for other pathogen-induced, age-dependent respiratory diseases.
