Function and expression of CD1d and invariant natural killer T-cell receptor in the cotton rat (Sigmodon hispidus).

The cotton rat (Sigmodon hispidus) belongs to the rodent family of Cricetidae and provides a powerful model to study the pathogenesis of human respiratory viruses and measles virus. Recent studies in other rodent models have suggested a role for invariant natural killer T (iNKT) cells in antiviral immunity and vaccination against respiratory virus infections. Using new experimental tools, we provide the first evidence for a functional CD1d cell molecule (crCD1d) and iNKT T-cell receptor in cotton rats. The crCD1d cDNA sequence was identified and crCD1d transductants showed that monoclonal antibody WTH-2 stains crCD1d as efficiently as mouse or rat CD1d. The expression of crCD1d was clearly weaker for thymocytes and B cells, and higher for T cells, which is different to what is found in murine species. The antigen-presenting capacity of crCD1d was demonstrated with crCD1d-immunoglobulin dimers loaded with the glycolipid PBS57, which bound iNKT T-cell receptors. Evidence for functional cotton rat iNKT cells was provided by detection of interferon-γ and interleukin-4 in cultures of splenocytes stimulated with PBS57 and α-galactosylceramide and by specific staining of about 0·2% of splenocytes with PBS57-loaded crCD1d dimers. Canonical AV14/AJ18 rearrangements were identified and found to contain multiple members of the AV14 (AV11) family. One of them was expressed and found to bind CD1d dimers. In summary, these data provide the first evidence for functional CD1d molecules and iNKT T-cell receptors in cotton rats and provide the tools to analyse them both in the cotton rat model of infectious diseases.

Complicated and uncomplicated S. aureus bacteraemia: an international Delphi survey among infectious diseases experts on definitions and treatment.

OBJECTIVES: Classification of Staphylococcus aureus bacteraemia (SAB) as 'complicated' or 'uncomplicated' and management of both is based on low-quality evidence. The aim of the study was to determine the degree of agreement among infectious diseases physician experts in the management of patients with SAB. METHODS: A stepwise RAND-modified Delphi procedure with two questionnaire rounds was performed. Four aspects of management in 22 clinical scenarios were addressed: (a) classification of SAB episodes; (b) value of combination therapy; and (c) timing of and (d) preferred antibiotics for oral stepdown therapy. RESULTS: Out of 90 approached experts, 33 (36.7%) from 14 different countries and 5 continents consented to participate. The experts considered any of the discussed implanted foreign material (with no evidence of infection), except for coronary artery stents, as relevant to the classification of a complicated SAB episode. Concerning antibiotic combination therapy, the experts strongly agreed that combination therapy with rifampicin is only relevant in patients with prosthetic valve endocarditis and prosthetic joint infection. The experts considered an oral stepdown therapy in patients with an uncomplicated SAB within 14 days and only thereafter in patients with a complicated SAB episode, but never in patients with prosthetic valve endocarditis. No single antibiotic of choice for oral stepdown therapy could be identified, neither for infections with methicillin-resistant S. aureus nor methicillin-susceptible S. aureus. DISCUSSION: The Delphi survey can help physicians in their day-to-day decision-making process, and it reveals open questions that must be investigated by further studies.