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.
Hayes
K S
KS
Faculty of Life Sciences, University of Manchester, Manchester, UK. kelly.hayes@manchester.ac.uk
Bancroft
A J
AJ
Grencis
R K
RK
D000818:Animals; D005260:Female; D020397:Goblet Cells / Q000276:immunology / Q000378:metabolism; D006729:Hormones, Ectopic / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D018793:Interleukin-13 / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D008643:Mesentery / Q000276:immunology; D051379:Mice; D008806:Mice, Inbred AKR; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D055262:Mucin-2; D009077:Mucins / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology* / Q000469:parasitology; D018418:Th2 Cells / Q000276:immunology* / Q000469:parasitology; D014257:Trichuriasis / Q000276:immunology*; D014258:Trichuris / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D006729:Hormones, Ectopic; D036341:Intercellular Signaling Peptides and Proteins; D018793:Interleukin-13; C524626:Muc2 protein, mouse; D055262:Mucin-2; D009077:Mucins; C486522:Retnlb protein, mouse; D014409:Tumor Necrosis Factor-alpha