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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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Subclass of B. pertussis–specific IgG in the serum 43 d after  respiratory infection of wildtype and gene disrupted mice. Serum IgG was  measured by B. pertussis–specific ELISA. Results are given as the geometric mean (±SE) ELISA titers from at least four mice determined in quadruplicate.
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Figure 4: Subclass of B. pertussis–specific IgG in the serum 43 d after respiratory infection of wildtype and gene disrupted mice. Serum IgG was measured by B. pertussis–specific ELISA. Results are given as the geometric mean (±SE) ELISA titers from at least four mice determined in quadruplicate.

Mentions: The contribution of antigen-specific B cells and specific Ig to the resolution of B. pertussis infection of humans and experimental animals is controversial (6–8). The development of the specific antibody response after aerosol challenge was characterized in normal mice and in mice with targeted gene disruptions. The results shown in Table II confirm that Ig−/− mice, which lack mature B cells, fail to mount an IgG antibody response. In contrast, wild-type C57BL/6 and 129Sv/Ev mice, as well as the IL-4−/− and IFN-γR−/− gene knockout mice develop B. pertussis-specific serum antibody by day 24 after challenge, which increases in titer until at least day 100. Higher antibody titers were observed early after infection in IFN-γR−/− mice, when compared with the wild-type strain. Conversely IL-4−/− mice produced lower titers of specific antibody than that observed in wild-type C57BL/6 mice at early time points. An examination of the antibody isotypes revealed that the predominant IgG subclass detected was IgG2a, with little or no IgG1, except in IFN-γR−/− mice which displayed higher titers of IgG2b and lower levels of IgG2a (Fig. 4). This pattern was consistent between analyses on serum samples recovered 24, 43, and 100 d after 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)

Subclass of B. pertussis–specific IgG in the serum 43 d after  respiratory infection of wildtype and gene disrupted mice. Serum IgG was  measured by B. pertussis–specific ELISA. Results are given as the geometric mean (±SE) ELISA titers from at least four mice determined in quadruplicate.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 4: Subclass of B. pertussis–specific IgG in the serum 43 d after respiratory infection of wildtype and gene disrupted mice. Serum IgG was measured by B. pertussis–specific ELISA. Results are given as the geometric mean (±SE) ELISA titers from at least four mice determined in quadruplicate.
Mentions: The contribution of antigen-specific B cells and specific Ig to the resolution of B. pertussis infection of humans and experimental animals is controversial (6–8). The development of the specific antibody response after aerosol challenge was characterized in normal mice and in mice with targeted gene disruptions. The results shown in Table II confirm that Ig−/− mice, which lack mature B cells, fail to mount an IgG antibody response. In contrast, wild-type C57BL/6 and 129Sv/Ev mice, as well as the IL-4−/− and IFN-γR−/− gene knockout mice develop B. pertussis-specific serum antibody by day 24 after challenge, which increases in titer until at least day 100. Higher antibody titers were observed early after infection in IFN-γR−/− mice, when compared with the wild-type strain. Conversely IL-4−/− mice produced lower titers of specific antibody than that observed in wild-type C57BL/6 mice at early time points. An examination of the antibody isotypes revealed that the predominant IgG subclass detected was IgG2a, with little or no IgG1, except in IFN-γR−/− mice which displayed higher titers of IgG2b and lower levels of IgG2a (Fig. 4). This pattern was consistent between analyses on serum samples recovered 24, 43, and 100 d after 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