Pulmonary clearance of Mycoplasma pulmonis in C57BL/6N and C3H/HeN mice

Abstract

In C57BL/6N and C3H/HeN mice known to be free of all murine pathogens and matched for age, sex, and environmental factors, pulmonary clearance was measured over a 72-h time period after exposure to infectious aerosols of 35S-labeled Mycoplasma pulmonis. Reduced clearance of M. pulmonis in C3H/HeN mice relative to C57BL/6N mice was primarily due to impaired mycoplasmacidal activity in the lungs of the C3H/HeN mice. The C3H/HeN mice also had a slightly slower rate of mechanical transport of radiolabel from the lungs in the first 4 h after infection relative to the C57BL/6N mice but not at any later times. By 72 h after infection (relative to 0 h, C3H/HeN mice had an over 4,000% (1.75 X 10(7) versus 4.30 X 10(5] increase in neutrophils and an over 18,000% (more than 2 orders of magnitude) increase in numbers of M. pulmonis recovered from mechanically disaggregated lungs. In contrast, C57BL/6N mice reduced the number of M. pulmonis present by over 83% (nearly 2 orders of magnitude) before any increase in inflammatory cells, which was only a slight increase in lymphocytes and macrophages at 24 h after infection. These results directly link decreased mycoplasmal pulmonary clearance in C3H/HeN mice with the increased susceptibility to, and severity of, murine respiratory mycoplasmosis observed in this strain. The resistance of C57BL/6N mice appears to be related to nonspecific host defense mechanisms responsible for limiting the extent of infection.

Mycoplasma pneumoniae Induces Host-Dependent Pulmonary Inflammation and Airway Obstruction in Mice

“…In a similar model using the mouse pathogenic mycoplasma species M. pulmonis, it was demonstrated that certain mouse strains differ markedly in resistance to infection and progression of disease with C3H/HeN mice being more susceptible than C57BL/6 mice (41). The resistance of C57BL/6 mice to M. pulmonis is thought to be related to nonspecific, innate intrapulmonary host immunity which limits the extent of infection (41,42). Cartner and coworkers have also investigated the response of various murine strains to infection with M. pulmonis by evaluating 17 inbred mouse strains, and found that resistance to murine mycoplasmosis is a complex trait controlled by multiple genes (43).…”

Clearance of different strains of Mycoplasma pulmonis from the respiratory tract of C3H/HeN mice

“…Experimental inoculations. The method of aerosolization of M. pulmonis and verification of organism viability has been described previously (9,25). Briefly, mice were exposed to aerosols generated with 107 to i09 M. pulmonis per ml in the nebulizer.…”

“…Calculation of physical clearance. Physical removal of radioactive label was expressed as a percentage of the mean disintegrations per minute at 0 h (immediately after infection) for each strain of mycoplasma in order to allow comparison among strains (25). pulmonis was calculated from the change in the CFU to disintegrations per minute ratio at each time point relative to the ratio at 0 h (ratio at each time point/ratio at time 0).…”

“…Statistical analysis. Mycoplasmas must be freshly grown to survive aerosolization (9,25). Therefore, the concentration of organisms and the radioactive labeling efficiency could not be known at the time of delivery of the aerosol.…”

“…It has been shown previously that C3H/HeN mice are highly susceptible to Mycoplasma pulmonis infection and disease (8). An aerosol model has been described previously (9), and pulmonary clearance of virulent M. pulmonis by C3H/HeN mice has been reported previously (25). In addition, it has been shown that M. pulmonis strains differ in virulence as lung pathogens (6,15).…”