The role of TNF-alpha in Trichuris muris infection I: influence of TNF-alpha receptor usage, gender and IL-13

Th1 and Th2 responses to the gut-dwelling nematode Trichuris muris have been well established in mouse models of infection, with Th2 responses clearly playing an important role in resistance. TNF-alpha has previously been shown to play an undefined role in resistance, although it is not a typical Th2 cytokine. However, the relative importance of the two TNF-alpha receptors, p55 and p75, has not previously been investigated. We demonstrate that p55 is the dominant TNF-alpha receptor during T. muris infection as p55-/- mice are more susceptible to infection than p75-/- mice. Moreover, p75 clearly plays a role in negatively regulating TNF-alpha. We also demonstrate that a gender difference influences the immune response of p55-/- and p75-/- mice in response to T. muris infection, with female mice fully expelling by day 35 post-infection (p.i.) and male mice harbouring chronic infections. Further, this gender difference can be reversed with recombinant IL-13 (rIL-13) in male gene-deficient mice or IL-13R2.Fc treatment in female gene-deficient mice.