Limits...
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.

Show MeSH

Related in: MedlinePlus

Course of B. pertussis respiratory infection in normal and  gene knockout mice. IL-4−/− and C57BL/6 (A), IFN-γR−/− and 129Sv/Ev  (B), and Ig−/− and C57BL/6 (C) mice were infected by aerosol with 2 ×  1010 CFU/ml B. pertussis, giving an initial colonization of 2–8 × 104 per  lung. Groups of mice were killed at intervals after challenge and the number of viable bacteria estimated by performing colony counts on individual lung homogenates. Results are representative from two experiments  and are presented as mean (±SE) CFU in the lungs estimated for three or  four mice at each time point.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2199147&req=5

Figure 3: Course of B. pertussis respiratory infection in normal and gene knockout mice. IL-4−/− and C57BL/6 (A), IFN-γR−/− and 129Sv/Ev (B), and Ig−/− and C57BL/6 (C) mice were infected by aerosol with 2 × 1010 CFU/ml B. pertussis, giving an initial colonization of 2–8 × 104 per lung. Groups of mice were killed at intervals after challenge and the number of viable bacteria estimated by performing colony counts on individual lung homogenates. Results are representative from two experiments and are presented as mean (±SE) CFU in the lungs estimated for three or four mice at each time point.

Mentions: To examine the role of Th1 and Th2 cytokines on the course of infection in the lungs, the kinetics of bacterial clearance was monitored by performing CFU counts on the lungs of wild-type and gene disrupted mice at intervals after challenge. Although IFN-γR−/− mice displayed an atypical disease which proved lethal in ∼30% of infected mice, the kinetics of bacterial clearance from the lungs of surviving animals was not significantly different from the wild-type 129Sv/Ev mice (Fig. 3). There was no significant difference in the kinetics of bacterial clearance from the lungs of IL-4−/− and the wild-type C57BL/6 mice (Fig. 3). We have previously reported that MHC and non-MHC differences between mouse strains influence murine survival in the B. pertussis intracerebral challenge model (11). Here we show that unlike BALB/c (H-2d) mice which reproducibly clear a respiratory challenge within 40 d (9), C57BL/6 and 129Sv/Ev (both H-2b) do not completely clear a respiratory challenge until up to 100 d after challenge (Fig. 3).


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)

Course of B. pertussis respiratory infection in normal and  gene knockout mice. IL-4−/− and C57BL/6 (A), IFN-γR−/− and 129Sv/Ev  (B), and Ig−/− and C57BL/6 (C) mice were infected by aerosol with 2 ×  1010 CFU/ml B. pertussis, giving an initial colonization of 2–8 × 104 per  lung. Groups of mice were killed at intervals after challenge and the number of viable bacteria estimated by performing colony counts on individual lung homogenates. Results are representative from two experiments  and are presented as mean (±SE) CFU in the lungs estimated for three or  four mice at each time point.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 3: Course of B. pertussis respiratory infection in normal and gene knockout mice. IL-4−/− and C57BL/6 (A), IFN-γR−/− and 129Sv/Ev (B), and Ig−/− and C57BL/6 (C) mice were infected by aerosol with 2 × 1010 CFU/ml B. pertussis, giving an initial colonization of 2–8 × 104 per lung. Groups of mice were killed at intervals after challenge and the number of viable bacteria estimated by performing colony counts on individual lung homogenates. Results are representative from two experiments and are presented as mean (±SE) CFU in the lungs estimated for three or four mice at each time point.
Mentions: To examine the role of Th1 and Th2 cytokines on the course of infection in the lungs, the kinetics of bacterial clearance was monitored by performing CFU counts on the lungs of wild-type and gene disrupted mice at intervals after challenge. Although IFN-γR−/− mice displayed an atypical disease which proved lethal in ∼30% of infected mice, the kinetics of bacterial clearance from the lungs of surviving animals was not significantly different from the wild-type 129Sv/Ev mice (Fig. 3). There was no significant difference in the kinetics of bacterial clearance from the lungs of IL-4−/− and the wild-type C57BL/6 mice (Fig. 3). We have previously reported that MHC and non-MHC differences between mouse strains influence murine survival in the B. pertussis intracerebral challenge model (11). Here we show that unlike BALB/c (H-2d) mice which reproducibly clear a respiratory challenge within 40 d (9), C57BL/6 and 129Sv/Ev (both H-2b) do not completely clear a respiratory challenge until up to 100 d after challenge (Fig. 3).

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