The role of TNF-alpha in Trichuris muris infection II: global enhancement of ongoing Th1 or Th2 responses.

Host resistance to Trichuris muris is driven by Th2 responses. However, TNF-alpha has also been shown to play a role in protection. As TNF-alpha has a variety of actions, the exact role of TNF-alpha in immunity to T. muris is yet to be established. Here we demonstrate that although blocking TNF-alpha has been shown to abrogate resistance, rTNF-alpha treatment does not promote resistance. Further, we show that TNF-alpha functions to enhance the ongoing immune response. AKR animals that typically respond to infection with a polarized Th1 response produce greater levels of Th1 cytokines when treated with TNF-alpha and BALB/c animals that normally respond with a polarized Th2 response produce higher levels of Th2 cytokines. Crucially, blocking TNF-alpha in the strong Th2 responder strain BALB/c does not prevent expulsion of T. muris, thus supporting its role as a biological enhancer. TNF-alpha does increase transcription of both IFN-gamma and IL-13 in vitro but can also act synergistically with IL-13 in vitro to promote production of RELMbeta, which has also been shown to play a role in resistance to T. muris. Thus, this data demonstrates that TNF-alpha acts to enhance an ongoing immune response but is not necessary for a strong protective Th2 response.