title: 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.
abstract: Rhodococcus equi is a facultative intracellular bacterial pathogen that causes pneumonia in foals and immunosuppressed humans. There are at least three virulence levels of R. equi and these pathogenicities are associated, in mice, with the presence of virulence plasmids. This study focused on cytokine secretion, in mice, in the course of a primary infection with sublethal doses of R. equi strains of different virulence levels (virulent, intermediately 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 clearance of virulent and intermediately virulent strains of R. equi. These cytokines were not detected in mice infected with avirulent R. equi. Deaths occurred among mice treated with monoclonal antibodies (mAbs) against either TNF or IFN-gamma prior to sublethal dose infection with virulent and intermediately virulent strains of R. equi, but not with avirulent R. equi. These results suggested that cytokine production depended largely on the virulence levels of R. equi: TNF and IFN-gamma were required early during infection with virulent R. equi to limit replication and clearance of bacteria within the organs, but they were not necessary for limiting infection with avirulent R. equi.
authors.affiliation: Department of Animal Hygiene, School of Veterinary Medicine and Animal Sciences, Kitasato University, Towada, Aomori 034-8628, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kasuga-Aoki
authors.forename: S
authors.initials: S
authors.lastname: Takai
authors.forename: Y
authors.initials: Y
authors.lastname: Sasaki
authors.forename: S
authors.initials: S
authors.lastname: Tsubaki
authors.forename: H
authors.initials: H
authors.lastname: Madarame
authors.forename: A
authors.initials: A
authors.lastname: Nakane
mesh_terms: D000193:Actinomycetales Infections / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006825:Hybridomas; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000032:analysis / Q000096:biosynthesis* / Q000276:immunology; D016753:Interleukin-10 / Q000032:analysis / Q000096:biosynthesis; D015847:Interleukin-4 / Q000032:analysis / Q000096:biosynthesis; D051379:Mice; D016929:Rhodococcus equi / Q000472:pathogenicity*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis* / Q000276:immunology; D014774:Virulence
chemical_list: D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma