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TAPEWORM EXAGGERATION OF TH2 COLITIS: INVOLVEMENT OF NK1.1⁺ CELLS AND EOSINOPHILS

MM Hunter¹, A Wang², DM McKay²
¹Intestinal Disease Research Programme, McMaster University, Hamilton, Ontario; ²Gastrointestinal Research Group, University of Calgary, Calgary, Alberta

We have shown that infection with the rat tapeworm Hymenolepis diminuta reduced the severity of DNBS-induced colitis (TH1-type) but increased the inflammation associated with oxazolone-induced colitis (TH2-type). NK T cell derived IL-13 is thought to be responsible for the oxazolone-induced pathology, and administration of an NK T cell depleting antibody will prevent this colitis. Here we assessed the impact of NK T cell depletion on the pro-colitic effect of H. diminuta infection in the oxazolone model of colitis. Male BALB/c mice (n=4) received 5 viable H. diminuta larvae followed 8 days later by intra-rectal oxazolone (ox; 3mg in 50% EtOH). Anti-NK1.1 antibody (20 ľg/100ľl 0.9% NaCl) was administered ip on days 1, 2, 5, 8 and 11. Mice were assessed 72-hours post-oxazolone, at which time colon length was recorded and portions of the colon processed for measurement of myeloperoxidase activity and histological assessment. As expected, mice that received oxazolone only showed signs of colitis which were enhanced by H. diminuta infection (Table 1). Neutralizing NK1.1 antibody blocked the oxazolone colitis but only partially prevented the inflammation cased by Ox + H. diminuta; the latter was associated with increased eosinophils and eosinophil peroxidase in the colon.

Treatment Clinical Score MPO Colon Length (mm) Damage Score
Control 0 ą 0^a 0.28 ą 0.07^a 109 ą 1.2^a 0 ą 0
Ox (3 mg, ir) + Ig 1.25 ą 0.3^b 1.94 ą 0.56^b 91 ą 3.1^b 3 ą 1.1
Ox + anti-NK1.1 0.5 ą 0.2^a 0.55 ą 0.28^a 105 ą 2^a 1.1 ą 0.2
Ox + H. diminuta 3.375 ą 0.9^c 4.01 ą 1^c 76 ą 5.5^c 8 ą 1
Ox + H. diminuta + anti-NK1.1 1.5 ą 0.8^b 0.96 ą 1^ab 96 ą 8.7^ab 4.17 ą 0.72
mean ą SEM; a-c, groups are significantly different, p<0.05;n=4; Ig = irrelevant isotype matched antibody

These results suggest that H. diminuta exaggeration of oxazolone is additive to NK1.1 cell activity and synergistic by the mobilization of an eosinophil response. Overall, these findings indicate that the underlying disease must be carefully characterized before any attempt at helminth therapy is made.
Funded by the CCFC

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Treatment	Clinical Score	MPO	Colon Length (mm)	Damage Score
Control	0 ą 0^a	0.28 ą 0.07^a	109 ą 1.2^a	0 ą 0
Ox (3 mg, ir) + Ig	1.25 ą 0.3^b	1.94 ą 0.56^b	91 ą 3.1^b	3 ą 1.1
Ox + anti-NK1.1	0.5 ą 0.2^a	0.55 ą 0.28^a	105 ą 2^a	1.1 ą 0.2
Ox + H. diminuta	3.375 ą 0.9^c	4.01 ą 1^c	76 ą 5.5^c	8 ą 1
Ox + H. diminuta + anti-NK1.1	1.5 ą 0.8^b	0.96 ą 1^ab	96 ą 8.7^ab	4.17 ą 0.72
mean ą SEM; a-c, groups are significantly different, p<0.05;n=4; Ig = irrelevant isotype matched antibody