Establishment of nematode infection despite increased Th2 responses and immunopathology after selective depletion of Foxp3+ cells.
Here, we show that Treg limit intestinal pathology during nematode infection and that they control the onset and magnitude of the anti-parasitic Th Th2 response. Using mice expressing the diphtheria toxin receptor under the control of the foxp3 locus, we removed Foxp3(+) Treg during the early phase of infection with Heligmosomoides polygyrus bakeri. Depletion of Treg in infected animals did not affect adult worm burden, but led to increased pathology at the site of infection. Infected, depleted mice displayed higher frequencies of activated CD4(+) T cells and increased levels of the Th2 cytokines IL-4 and IL-13. The stronger parasite-specific Th2 response was accompanied by higher levels of IL-10. Only a moderate change in Th1 (IFN-gamma) reactivity was detected in worm-infected, Treg-depleted mice. Furthermore, we detected an accelerated onset of parasite-specific Th2 and IL-10 responses in the transient absence of Foxp3(+) Treg. However, adult worm burdens were not affected by the increased Th2-reactivity in Treg-depleted mice. Hence, our data show that Treg restrict the onset and strength of Th2 responses during intestinal worm infection, while increasing primary Th2 responses does not necessarily lead to killing of larvae or accelerated expulsion of adult worms.
Rausch
Sebastian
S
Department of Molecular Parasitology, Humboldt-University of Berlin, Berlin, Germany. sebastian.rausch@hu-berlin.de
Huehn
Jochen
J
Loddenkemper
Christoph
C
Hepworth
Matthew R
MR
Klotz
Christian
C
Sparwasser
Tim
T
Hamann
Alf
A
Lucius
Richard
R
Hartmann
Susanne
S
D000818:Animals; D051858:Forkhead Transcription Factors / Q000276:immunology*; D006369:Heligmosomatoidea; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017206:Strongylida Infections / Q000276:immunology* / Q000503:physiopathology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse