The effect of experimental infection with Rhodococcus equi on immunodeficient mice

Abstract

To investigation the pathogenesis of respiratory lesions caused by the facultative intracellular pathogen, Rhodococcus equi, pulmonary clearance was compared in four groups of genetically defined mice, chosen for their specifi deficits in immune and inflammatory responses. Complement-deficient A/J, immunodeficient nu/nu (nude), scid/scid.bg/bg (SCUD/beige), C57BI/6J.bg/bg (beige) and normal Swiss mice (SW) received approximately 10 7 R. equi intranasally on day 0. Bacterial clearance was assessed in lung, liver and spleen on days 1, 4, 7 and 14. Pulmonary clearance was not significantly different between SW and A/J mice. Beige mice cleared R. equi more rapidly and completely than A/J and SW, indicating that deficits in phagocytic and NK cell function associated with the bg/bg gene did not compromise clearance. Pulmonary clearance in immunodeficient SCID/beige mice paralleled that of the SW and A/J mice initially but bacterial proliferation produced significant differences from SW mice at day 14. Nude were unable to clear R. equi from day 1, resulting in th death of two nude mice at day 11. Both SCID/beige and nude mice developed severe pyrogranulomatous bronchopneumonia, whereas A/J and SW mice developed transient pulmonary lesions. Beige mice developed minimal lung lesions. Significant systematic bacterial proliferation occurred only in nude and SCID/beige mice. We conclude that deficiencies in complement components, phagocytic and NK cells do not impair the pulmonary clearance of R. equi but that a competent cellular immune system is required to prevent pneumonia and death. The difference in early phase pulmonary clearance in nude and SCID/beige mice indicates two phases are important for clearance. An acapsular mutant of R. equi was completely cleared from the lungs of SCID/beige mice suggesting an important role for the capsule in virulence for mice.