Cytotoxic CD8+ T cell ablation enhances the capacity of regulatory T cells to delay viral elimination in Theiler's murine encephalomyelitis.

Theiler's murine encephalomyelitis (TME) of susceptible mouse strains is a commonly used infectious animal model for multiple sclerosis. The study aim was to test the hypothesis whether cytotoxic T cell responses account for the limited impact of regulatory T cells on antiviral immunity in TME virus-induced demyelinating disease (TMEV-IDD) resistant C57BL/6 mice. TME virus-infected C57BL/6 mice were treated with (i) interleukin-2/-anti-interleukin-2-antibody-complexes to expand regulatory T cells ("Treg-expansion"), (ii) anti-CD8-antibodies to deplete cytotoxic T cells ("CD8-depletion") or (iii) with a combination of Treg-expansion and CD8-depletion ("combined treatment") prior to infection. Results showed that "combined treatment", but neither sole "Treg-expansion" nor "CD8-depletion," leads to sustained hippocampal infection and virus spread to the spinal cord in C57BL/6 mice. Prolonged infection reduces myelin basic protein expression in the spinal cord together with increased accumulation of ß-amyloid precursor protein in axons, characteristic of myelin loss and axonal damage, respectively. Chronic spinal cord infection upon "combined treatment" was also associated with increased T and B cell recruitment, accumulation of CD107b+ microglia/macrophages and enhanced mRNA expression of interleukin (IL)-1α, IL-10 and tumor necrosis factor α. In conclusion, data revealed that the suppressive capacity of Treg on viral elimination is efficiently boosted by CD8-depletion, which renders C57BL/6 mice susceptible to develop chronic neuroinfection and TMEV-IDD.

Fatal nocardiosis in a dog caused by multiresistant Nocardia veterana.

Among pathogenic Nocardia species in humans and animals, infections caused by Nocardia (N.) veterana have rarely been described and so far, all non-human cases are linked to bovine mastitis in Brazil. The aim of this study was to identify the causative microorganism involved in the death of a three-month-old dog suffering from dyspnea and neurological deficits ante mortem. Pathomorphological investigation revealed (pyo-)granulomatous lesions in various organs. Bacteriological examination was performed and the respective bacteria were subjected to matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS), 16S rDNA sequencing, and antimicrobial susceptibility testing by broth microdilution. Gram-staining and colony morphology suggested the presence of an actinomycete which was identified as N. veterana by MALDI-TOF MS. This identification was confirmed by 16S rDNA sequence analysis. Distemper-associated immunosuppression may have played a role in the pathogenesis of systemic nocardiosis in this dog. Retrospective analysis of the antimicrobial susceptibility status showed that the N. veterana isolate was multiresistant and displayed high minimal inhibitory concentrations to all antimicrobial agents used for the dog's therapy. To the best of our knowledge, this is the first report of a systemic nocardiosis caused by N. veterana in a dog with a concurrent canine distemper virus infection.