Tumour necrosis factor and interferon-gamma are required in host resistance against virulent Rhodococcus equi infection in mice: Cytokine production depends on the virulence levels of R-equi

Rhodococcus equi is a facultative intracellular bacterial pathogen that cau ses pneumonia in foals and immunosuppressed humans. There are at least thre e virulence levels of R. equi and these pathogenicities are associated, in mice, with the presence of virulence plasmids. This study focused on cytoki ne secretion, in mice, in the course of a primary infection with sublethal doses of R. equi strains of different virulence levels (virulent, intermedi ately virulent and avirulent). Tumour necrosis factor (TNF) and interferon- gamma (IFN-gamma), but not interleukin-4 (IL-4) and interleukin-10 (IL-10), were induced endogenously in mice in relation to the multiplication and cl earance of virulent and intermediately virulent strains of R. equi. These c ytokines were not detected in mice infected with avirulent R. equi. Deaths occurred among mice treated with monoclonal antibodies (mAbs) against eithe r TNF or IFN-gamma prior to sublethal dose infection with virulent and inte rmediately virulent strains of R. equi, but not with avirulent R. equi. The se results suggested that cytokine production depended largely on the virul ence levels of R. equi: TNF and IFN-gamma were required early during infect ion with virulent R. equi to limit replication and clearance of bacteria wi thin the organs, but they were not necessary for limiting infection with av irulent R. equi.