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Atypical disease after Bordetella pertussis respiratory infection of mice with targeted disruptions of interferon-gamma receptor or immunoglobulin mu chain genes.

Mahon BP, Sheahan BJ, Griffin F, Murphy G, Mills KH - J. Exp. Med. (1997)

Bottom Line: Viable virulent bacteria were detected in the blood and livers of diseased animals.An examination of the course of infection in the lung of IFN-gamma receptor-deficient, IL-4-deficient and wild-type mice demonstrated that lack of functional IFN-gamma or IL-4, cytokines that are considered to play major roles in regulating the development of Th1 and Th2 cells, respectively, did not affect the kinetics of bacterial elimination from the lung.In contrast, B cell-deficient mice developed a persistent infection and failed to clear the bacteria after aerosol inoculation.

View Article: PubMed Central - PubMed

Affiliation: Infection and Immunity Group, Department of Biology, National University of Ireland, Maynooth, County Kildare, Ireland.

ABSTRACT
Using a murine respiratory challenge model we have previously demonstrated a role for Th1 cells in natural immunity against Bordetella pertussis, but could not rule out a role for antibody. Here we have demonstrated that B. pertussis respiratory infection of mice with targeted disruptions of the genes for the IFN-gamma receptor resulted in an atypical disseminated disease which was lethal in a proportion of animals, and was characterized by pyogranulomatous inflammation and postnecrotic scarring in the livers, mesenteric lymph nodes and kidneys. Viable virulent bacteria were detected in the blood and livers of diseased animals. An examination of the course of infection in the lung of IFN-gamma receptor-deficient, IL-4-deficient and wild-type mice demonstrated that lack of functional IFN-gamma or IL-4, cytokines that are considered to play major roles in regulating the development of Th1 and Th2 cells, respectively, did not affect the kinetics of bacterial elimination from the lung. In contrast, B cell-deficient mice developed a persistent infection and failed to clear the bacteria after aerosol inoculation. These findings demonstrate an absolute requirement for B cells or their products in the resolution of a primary infection with B. pertussis, but also define a critical role for IFN-gamma in containing bacteria to the mucosal site of infection.

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Related in: MedlinePlus

Survival of IFN-γR−/− mice after B. pertussis challenge. In  one experiment groups of 24 IFN-γR−/− (○) or 24 wild-type 129Sv/Ev  (□) mice were aerosol challenged with B. pertussis which resulted in an  inoculum of 6 × 104 CFU/lung, determined from a sample group killed  2 h after challenge. In a separate experiment 6 IFN-γR−/− mice (•) received a higher dose challenge, which resulted in 1 × 106 CFU/lung 2 h  after challenge. Six wild-type 129Sv/Ev mice (▪) exposed to the higher  dose of bacteria all survived the challenge (displayed offset for clarity).
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Figure 1: Survival of IFN-γR−/− mice after B. pertussis challenge. In one experiment groups of 24 IFN-γR−/− (○) or 24 wild-type 129Sv/Ev (□) mice were aerosol challenged with B. pertussis which resulted in an inoculum of 6 × 104 CFU/lung, determined from a sample group killed 2 h after challenge. In a separate experiment 6 IFN-γR−/− mice (•) received a higher dose challenge, which resulted in 1 × 106 CFU/lung 2 h after challenge. Six wild-type 129Sv/Ev mice (▪) exposed to the higher dose of bacteria all survived the challenge (displayed offset for clarity).

Mentions: Respiratory infection with B. pertussis proved lethal in a number of IFN-γR−/− mice, particularly in mice younger than 8 wk and those that received a high challenge inoculum (Fig. 1 and data not shown). Death appeared to result from organ failure associated with disseminating disease; B. pertussis infected IFN-γR−/− mice showed abnormal pathology not observed in the wild-type 129Sv/Ev mice. Furthermore, IFN-γR−/− mice that survived the challenge frequently showed overt lesions, visible macroscopically, in the liver, lungs, kidneys, spleen, and mesentery. All wild-type 129Sv/Ev mice (54 mice, 6 experiments) challenged with the same inoculum of bacteria survived the infection and lesions were confined to the lungs. All Ig−/− and IL-4−/− or C57BL/6 mice survived more than 20 wk after B. pertussis challenge.


Atypical disease after Bordetella pertussis respiratory infection of mice with targeted disruptions of interferon-gamma receptor or immunoglobulin mu chain genes.

Mahon BP, Sheahan BJ, Griffin F, Murphy G, Mills KH - J. Exp. Med. (1997)

Survival of IFN-γR−/− mice after B. pertussis challenge. In  one experiment groups of 24 IFN-γR−/− (○) or 24 wild-type 129Sv/Ev  (□) mice were aerosol challenged with B. pertussis which resulted in an  inoculum of 6 × 104 CFU/lung, determined from a sample group killed  2 h after challenge. In a separate experiment 6 IFN-γR−/− mice (•) received a higher dose challenge, which resulted in 1 × 106 CFU/lung 2 h  after challenge. Six wild-type 129Sv/Ev mice (▪) exposed to the higher  dose of bacteria all survived the challenge (displayed offset for clarity).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2199147&req=5

Figure 1: Survival of IFN-γR−/− mice after B. pertussis challenge. In one experiment groups of 24 IFN-γR−/− (○) or 24 wild-type 129Sv/Ev (□) mice were aerosol challenged with B. pertussis which resulted in an inoculum of 6 × 104 CFU/lung, determined from a sample group killed 2 h after challenge. In a separate experiment 6 IFN-γR−/− mice (•) received a higher dose challenge, which resulted in 1 × 106 CFU/lung 2 h after challenge. Six wild-type 129Sv/Ev mice (▪) exposed to the higher dose of bacteria all survived the challenge (displayed offset for clarity).
Mentions: Respiratory infection with B. pertussis proved lethal in a number of IFN-γR−/− mice, particularly in mice younger than 8 wk and those that received a high challenge inoculum (Fig. 1 and data not shown). Death appeared to result from organ failure associated with disseminating disease; B. pertussis infected IFN-γR−/− mice showed abnormal pathology not observed in the wild-type 129Sv/Ev mice. Furthermore, IFN-γR−/− mice that survived the challenge frequently showed overt lesions, visible macroscopically, in the liver, lungs, kidneys, spleen, and mesentery. All wild-type 129Sv/Ev mice (54 mice, 6 experiments) challenged with the same inoculum of bacteria survived the infection and lesions were confined to the lungs. All Ig−/− and IL-4−/− or C57BL/6 mice survived more than 20 wk after B. pertussis challenge.

Bottom Line: Viable virulent bacteria were detected in the blood and livers of diseased animals.An examination of the course of infection in the lung of IFN-gamma receptor-deficient, IL-4-deficient and wild-type mice demonstrated that lack of functional IFN-gamma or IL-4, cytokines that are considered to play major roles in regulating the development of Th1 and Th2 cells, respectively, did not affect the kinetics of bacterial elimination from the lung.In contrast, B cell-deficient mice developed a persistent infection and failed to clear the bacteria after aerosol inoculation.

View Article: PubMed Central - PubMed

Affiliation: Infection and Immunity Group, Department of Biology, National University of Ireland, Maynooth, County Kildare, Ireland.

ABSTRACT
Using a murine respiratory challenge model we have previously demonstrated a role for Th1 cells in natural immunity against Bordetella pertussis, but could not rule out a role for antibody. Here we have demonstrated that B. pertussis respiratory infection of mice with targeted disruptions of the genes for the IFN-gamma receptor resulted in an atypical disseminated disease which was lethal in a proportion of animals, and was characterized by pyogranulomatous inflammation and postnecrotic scarring in the livers, mesenteric lymph nodes and kidneys. Viable virulent bacteria were detected in the blood and livers of diseased animals. An examination of the course of infection in the lung of IFN-gamma receptor-deficient, IL-4-deficient and wild-type mice demonstrated that lack of functional IFN-gamma or IL-4, cytokines that are considered to play major roles in regulating the development of Th1 and Th2 cells, respectively, did not affect the kinetics of bacterial elimination from the lung. In contrast, B cell-deficient mice developed a persistent infection and failed to clear the bacteria after aerosol inoculation. These findings demonstrate an absolute requirement for B cells or their products in the resolution of a primary infection with B. pertussis, but also define a critical role for IFN-gamma in containing bacteria to the mucosal site of infection.

Show MeSH
Related in: MedlinePlus