T-box transcription-factor-deficient mice display increased joint pathology and failure of infection control during staphylococcal arthritis.

• To study the impact of T-box transcription factor (T-bet) on initiation and progression of Staphylococcus aureus sepsis and arthritis, T-bet-deficient mice (T-bet(-/-)) and their wild-type controls (T-bet(+/+)) were intravenously inoculated with 8 x 10(6) S. aureus. Already 48 h after inoculation of S. aureus, T-bet-deficient mice displayed increased frequency (62% versus 19%, P = 0.002) as well as severity of arthritis compared with wild-type controls. The bacterial counts were significantly increased in T-bet(-/-) mice compared with T-bet(+/+) as measured in kidneys 72 h after the inoculation (4.3 +/- 1.8 x 10(7) versus 3.2 +/- 3.2 x 10(6) colony-forming units (CFU); P = 0.003). As expected, T-bet-deficient mice displayed significantly decreased production of IFN-gamma (10-15-fold) at 24 and 72 h after bacterial inoculation compared with wild-type mice. Interestingly, in the absence of T-bet, serum IL-4 was decreased at 24 h. IL-6 did not differ at early stage of infection but was sixfold increased in T-bet(-/-) mice over T-bet(+/+) animals at 72 h postinoculation. Ten days after the inoculation, T-bet(-/-) mice still displayed significantly more pronounced weight loss and increased serum IL-6 levels, probably due to increased bacterial burden compared with T-bet(+/+) mice. The cumulative mortality was 19% in T-bet mice (5/27) and 0% (0/27) in control animals (P = 0.05). In conclusion, T-bet plays an important role in early response to S. aureus infection, protecting against bacterial accumulation, cachexia and septic death. Furthermore T-bet downregulates joint inflammation in the early phase of disease.

Nyckelord

Animals

Arthritis

Infectious

immunology

metabolism

microbiology

pathology

Body Weight

Colony Count

Microbial

Interferon Type II

blood

Interleukin-4

blood

Interleukin-6

blood

Joints

pathology

Kidney

microbiology

Mice

Mice

Inbred C57BL

Sepsis

immunology

metabolism

microbiology

pathology

Staphylococcal Infections

immunology

metabolism

microbiology

pathology

Staphylococcus aureus

growth & development

T-Box Domain Proteins

Transcription Factors

deficiency

physiology

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)