Abstract
Conflicting data has emerged regarding a role for eosinophils in IgA production, with some reports that eosinophils support both secretory and circulating IgA levels during homeostasis. Previous studies have compared antibody levels between wildtype and eosinophil-deficient mice, but these mice were obtained from different commercial vendors and/or were not littermates. Thus, the possibility remains that extrinsic environmental factors, rather than an intrinsic lack of eosinophils, are responsible for the reports of reduced IgA in eosinophil-deficient mice. Here we used wild-type and eosinophil-deficient (ΔdblGATA) mice that were purchased from a single vendor, subsequently bred in-house and either co-housed as adults, co-reared from birth or raised as littermates. We found no differences in the levels of secretory IgA or in the numbers of small intestinal IgA-producing plasma cells between wild-type and ΔdblGATA mice, demonstrating that under controlled steady-state conditions eosinophils are not essential for the maintenance of secretory IgA in the intestinal tract. While we found that levels of IgM and IgE were significantly elevated in the serum of ΔdblGATA mice compared to co-reared or co-housed wild-type mice, no significant differences in these or other circulating antibody isotypes were identified between genotypes in littermate-controlled experiments. Our results demonstrate that eosinophils are not required to maintain secretory or circulating IgA production and the absence of eosinophils does not impact circulating IgG1, IgG2b, IgM, or IgE levels during homeostasis. These findings emphasize the importance of optimally controlling rearing and housing conditions throughout life between mice of different genotypes.
Highlights
Eosinophils have been regarded as type 2 effector cells during both helminth infection and allergic inflammation [1,2,3,4,5]
While some groups have reported a reduction in fecal sIgA [10], small intestinal sIgA and circulating IgA levels [9, 10] in eosinophil-deficient mice compared to wild-type mice, others have detected no differences [7, 11]
A recent study found that while fecal sIgA was significantly reduced in dblGATA mice compared to wild-type mice, sIgA levels normalized following a period of co-housing wild-type and dblGATA female mice in a single cage [12]
Summary
Eosinophils have been regarded as type 2 effector cells during both helminth infection and allergic inflammation [1,2,3,4,5]. Two independent studies have reported a strict requirement for eosinophils in the maintenance of IgA-producing plasma cells in the small intestine with reduced secretory and serum IgA levels found in eosinophil-deficient mice [9, 10]. Despite these findings, other studies have reported no difference in secretory or serum IgA levels between wild-type and eosinophildeficient mice [7, 11] and recently, reported differences in IgA levels between wild-type and eosinophil-deficient mice have been attributed to bacterial microbiota compositional differences rather than due to an intrinsic absence of eosinophils [12]. Similar contradictions in published literature exist regarding the function of homeostatic eosinophils in the bone marrow: an initial report found that eosinophils are required for bone marrow-resident plasma cell survival [13], while later studies have demonstrated that eosinophils are not required to carry out this function [14, 15]
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