Identification of an interleukin (IL)-25-dependent cell population that provides IL-4, IL-5, and IL-13 at the onset of helminth expulsion.
Type 2 immunity, which involves coordinated regulation of innate and adaptive immune responses, can protect against helminth parasite infection, but may lead to allergy and asthma after inappropriate activation. We demonstrate that il25(-/-) mice display inefficient Nippostrongylus brasiliensis expulsion and delayed cytokine production by T helper 2 cells. We further establish a key role for interleukin (IL)-25 in regulating a novel population of IL-4-, IL-5-, IL-13-producing non-B/non-T (NBNT), c-kit+, FcepsilonR1- cells during helminth infection. A deficit in this population in il25(-/-) mice correlates with inefficient N. brasiliensis expulsion. In contrast, administration of recombinant IL-25 in vivo induces the appearance of NBNT, c-kit+, FcepsilonR1- cells and leads to rapid worm expulsion that is T and B cell independent, but type 2 cytokine dependent. We demonstrate that these IL-25-regulated cells appear rapidly in the draining lymph nodes, implicating them as a source of type 2 cytokines during initiation of worm expulsion.
Fallon
Padraic G
PG
Department of Biochemistry, Trinity College, Dublin 2, Ireland.
Ballantyne
Sarah J
SJ
Mangan
Niamh E
NE
Barlow
Jillian L
JL
Dasvarma
Ayan
A
Hewett
Duncan R
DR
McIlgorm
Ann
A
Jolin
Helen E
HE
McKenzie
Andrew N J
AN
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D001491:Basophils / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000145:classification; D018793:Interleukin-13 / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D015848:Interleukin-5 / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D007378:Interleukins / Q000008:administration & dosage / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009559:Nippostrongylus / Q000276:immunology*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D017455:Receptors, IgE / Q000172:deficiency; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism; D017206:Strongylida Infections / Q000276:immunology* / Q000469:parasitology*; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism
D016207:Cytokines; D018793:Interleukin-13; D015848:Interleukin-5; D007378:Interleukins; C442281:Mydgf protein, mouse; D017455:Receptors, IgE; D011994:Recombinant Proteins; D015847:Interleukin-4; D019009:Proto-Oncogene Proteins c-kit