Gastrointestinal nematode expulsion in IL-4 knockout mice is IL-13 dependent.
Female IL-4 knockout (KO) mice on a C57BL/6 background (F4KOC57) are susceptible to infection with the cecal-dwelling nematode Trichuris muris whereas wild-type C57BL/6 mice are resistant and expel the parasite. In this study we show that in sharp contrast, female IL-4 KO mice on a BALB/c background (F4KOB/c) are resistant to infection as are wild-type BALB/c mice. Although susceptible F4KOC57 make negligible levels of all type 2 cytokines, resistant F4KOB/c were capable of producing significant levels of antigen-specific IL-13 (a cytokine shown to be critical in resistance to T. muris). To examine if the IL-13 in F4KOB/c mice was of functional importance, it was neutralized in vivo using a fusion protein, A25 (sIL-13 R.Fc). The results presented here clearly demonstrate that neutralization of IL-13 in vivo did indeed prevent T. muris expulsion in normally resistant F4KOB/c mice. In addition, administration of recombinant mouse IL-13 to normally susceptible male IL-4KO BALB/c mice (M4KOB/c) caused an 87.85 % reduction in worm burden. Collectively, these data show that IL-13 is important in the poorly understood effector mechanisms resulting in the expulsion of T. muris from the gut. Moreover, the present data highlight the functional importance of gender and background strain in interpretation of studies using gene-targeted animals.
Bancroft
A J
AJ
School of Biological Sciences, University of Manchester, GB. abancrof@fs1.scg.man.ac.uk
Artis
D
D
Donaldson
D D
DD
Sypek
J P
JP
Grencis
R K
RK
D000818:Animals; D000909:Antibodies, Helminth / Q000097:blood; D004198:Disease Susceptibility; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000097:blood; D018793:Interleukin-13 / Q000096:biosynthesis / Q000276:immunology*; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D015848:Interleukin-5 / Q000096:biosynthesis; D016906:Interleukin-9 / Q000096:biosynthesis; D007411:Intestinal Diseases, Parasitic / Q000276:immunology* / Q000469:parasitology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009500:Neutralization Tests; D014257:Trichuriasis / Q000276:immunology* / Q000469:parasitology; D014258:Trichuris / Q000276:immunology
D000909:Antibodies, Helminth; D007074:Immunoglobulin G; D018793:Interleukin-13; D015848:Interleukin-5; D016906:Interleukin-9; D015847:Interleukin-4; D007371:Interferon-gamma