Age-dependent natural killer cell and interferon γ deficits contribute to severe pertussis in infant mice

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 resp...

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Published in:Journal of leukocyte biology 2024-05, Vol.115 (6), p.1143-1153
Main Authors: Mitchell, Ashley E, Scanlon, Karen M, Flowers, Emily M, Jordan, Cassandra M, Tibbs, Ellis J, Bukowski, Alicia, Gallop, Danisha, Carbonetti, Nicholas H
Format: Article
Language:English
Subjects:
Adoptive Transfer
Age Factors
Aging - immunology
Animals
Animals, Newborn
Bordetella pertussis - immunology
Disease Models, Animal
Interferon-gamma - metabolism
Killer Cells, Natural - immunology
Lung - immunology
Lung - microbiology
Lung - pathology
Mice
Mice, Inbred C57BL
Whooping Cough - immunology
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container_title Journal of leukocyte biology
container_volume 115
creator Mitchell, Ashley E
Scanlon, Karen M
Flowers, Emily M
Jordan, Cassandra M
Tibbs, Ellis J
Bukowski, Alicia
Gallop, Danisha
Carbonetti, Nicholas H
description 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.
doi_str_mv 10.1093/jleuko/qiae020
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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. 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source Oxford University Press Journals
subjects Adoptive Transfer
Age Factors
Aging - immunology
Animals
Animals, Newborn
Bordetella pertussis - immunology
Disease Models, Animal
Interferon-gamma - metabolism
Killer Cells, Natural - immunology
Lung - immunology
Lung - microbiology
Lung - pathology
Mice
Mice, Inbred C57BL
Whooping Cough - immunology
title Age-dependent natural killer cell and interferon γ deficits contribute to severe pertussis in infant mice
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