Role for interleukin-3 (IL-3) in mast cell and basophil development and parasite immunity revealed by IL-3-deficient mice

We used IL-3 -/- mice to assess the role of IL-3 in mast cell (MC) and basophil development and parasite immunity. IL-3 -/- mice developed normal numbers of tissue MCs and bone marrow (BM) basophils under physiological conditions, and showed no impairment in the tissue MC hyperplasia induced by treatment with stem cell actor (SCF) in vivo. However, fewer (∼11 fold less) MCs developed from IL-3 -/- BM cells than from IL-3 +/+ BM cells cultured 3 wks with SCF; no such differences was seen in cultures with SCF plus exogenous IL-3. IL-3 -/- mice infected with the nematode Strongyloides venezuelensis (S.v.), exhibited a significantly delayed (by 2-3 d) expulsion of the adult worms and prolonged production of the parasite's eggs, in comparison with IL-3 +/+ mice; no such differences were observed in the IL-3 -/- vs. +/+ mice infected with Nippostrongylus brasiliensis (N.b.). Either S.v. or N.b. infection induced a significant increase in BM basophils in IL-3 +/+ mice but not IL-3 -/- mice. IL-3 was also required for essentially all of the increases in MCs which developed in the ileum and spleen, and for a substantial proportion (50-90%) of the jejunal MC hyperplasia in S.v.- or N.b.-infected mice. By contrast, intestinal, blood, and BM eosinophil levels were comparable between IL-3 +/+ and IL-3 -/- infected mice. To examine S.v. infection in mice which both virtually lack MCs at baseline and can not make IL-3, we produced Kit^W//Kit^W-v, IL-3 -/- mice. These mice, compared to Kit^W/Kit^W-v, IL-3 +/+ mice, exhibited a much more profound defect in their ability to reject S.v. (up to 5 wks longer to expel adult worms), little or no increase in BM basophil levels, and dramatically reduced levels of jejunal, ileal, and splenic MCs. These findings show that IL-3 importantly contributes to both S.v.- and N.b.-induced MC hyperplasia and enhanced basophil development, and helps to maintain normal host immunity to S.v. Our data also indicate that IL-3 and SCF may express overlapping and/or synergistic roles in maintaining an adequate immune response to S.v.