Mice lacking T cell intrinsic expression of MyD88, an important adapter molecule in non-cognate T cell stimulation, exhibit higher bacterial burdens after infection with Salmonella, Chlamydia or Brucella. Overall, these data show that both IL-18R and DR3 are critical for non-cognate stimulation of Th1 cells and that this response is important for protection against intracellular bacteria. The gene discussed is TNFRSF25; the disease is infection.