The role of TNF-α in Trichuris muris infection II: global enhancement ofongoing Th1 or Th2 responses

Authors: HAYES, K. S.; BANCROFT, A. J.; GRENCIS, R. K.

Source: Parasite Immunology, Volume 29, Number 11, November 2007 , pp. 583-594(12)

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Abstract:

SUMMARY

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

Keywords: RELMβ; TNF-α; Trichuris muris

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1365-3024.2007.00980.x

Publication date: 2007-11-01