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Signal transducers and activators of transcription (STAT) 1 is a key transcription factor involved in innate and adaptive immune responses by governing the responses to interferons (IFNs) type I, II and III. In order to elucidate the cell type specific contributions of STAT1 to the host response to viral infections our lab generated conditional Stat1 mice. Cytomegalovirus (CMV) can trigger severe disease in immune suppressed individuals, is a frequent cause of congenital birth defects and still represents a major problem in health care. Immunity to acute and persistent CMV infection is intensively studied with respect natural killer (NK) and T cell function. Systemic STAT1 is required for defence against CMV but little is known about the contribution of STAT1 and innate immune cell function. Stat1ΔLysz mice showed highly efficient Stat1 allele depletion efficiencies in the myeloid compartment. Challenges of Stat1ΔLysz with various amounts of MCMV revealed no apparent effect of myeloid STAT1 to survival compared to wildtype mice. However, Stat1ΔLysz mice were deficient to restrict viral load in various organs and showed a high persistence of MCMV in salivary glands. With respect to early infection and viral spread we investigate cytokine expression and response activities, including cell type specific STAT activation. With respect to MCMV persistence we test the requirement of myeloid STAT1 for the activation of CD4+ and CD8+ T cells. This work was funded by the Austrian Science Fund (FWF) IAI DK W1212 and FWF SFB F28.

Partial reverse transcriptase sequencing of 16S rRNA from Mobiluncus curtisii and M. mulieris clearly indicate that the genus Mobiluncus is not a member of the Bacteroidaceae but belongs to the order Actinomycetales. The highest degree of relationship is found with the genus Actinomyces which is supported by the presence of common physiological properties.

To assess the role of the Janus kinase (Jak) family member Tyk2, we have generated Tyk2 -/- mice. In contrast to other Jaks, where inactivation leads to a complete loss of the respective cytokine receptor signal, Tyk2 -/- mice display reduced responses to IFNα/β and IL-12 and a selective deficiency in Stat3 activation in these pathways. Unexpectedly, IFNγ signaling is also impaired in Tyk2 -/- mice. Tyk2 -/- macrophages fail to produce nitric oxide upon lipopolysaccharide induction. Tyk2 -/- mice are unable to clear vaccinia virus and show a reduced T cell response after LCMV challenge. These data imply a selective contribution of Tyk2 to the signals triggered by various biological stimuli and cytokine receptors.