Littermate-Controlled Experiments Reveal Eosinophils Are Not Essential for Maintaining Steady-State IgA and Demonstrate the Influence of Rearing Conditions on Antibody Phenotypes in Eosinophil-Deficient Mice

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 (dblGATA) 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 dblGATA 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 dblGATA 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.

Eosinophils mediate SIgA production triggered by TLR2 and TLR4 to control Ascaris suum infection in mice

“…Our findings corroborate the data by FitzPatrick et al (2020), who described high levels of total SIgA under natural conditions and without infection in the absence of eosinophils [41]. However, we also found that eosinophils are essential for the maintenance of high levels of this immunoglobulin after infection with A. suum, corroborating the findings of previous studies [32,[44][45][46].…”

“…Moreover, a local eosinophilic response may also induce an increased number of eosinophils in remote sites [ 76 ]. Although some variations in basal SIgA levels have been observed in non-infected mice before, the literature suggests that variations in the native microbiota are natural [ 41 ]. It has also been reported that WT BALB/c and WT C57BL/6 mice strains differ in polyreactive IgA abundance and specificity, as well as in microbiota diversity [ 77 ].…”

“…These include potent eosinophil degranulation, helminth larvae entrapment, phagocytosis mediated by alternative complement cascade activation, and neutralization of proteins secreted/excreted by the parasite [7]. Although recent studies have shown that eosinophils are not necessary to maintain IgA levels in the absence of infection [41][42][43], eosinophil-deficient mouse models show a reduction in the number of plasma cells, IgA and SIgA levels in the intestinal lamina propria [32,[44][45][46].…”

Fantastic IgA plasma cells and where to find them

“…As such and like in other known effector niches, secreted factors and cellular interactions synergistically contribute to IgA + PC survival in the LP. Moreover, eosinophil‐deficient mice have been shown to harbor an altered microbiota which may also explain why these mice have less IgA + PC 51,52 …”

Maintenance of quiescent immune memory in the bone marrow

“…It has been postulated that eosinophilic granulocytes may be essential for plasma cell persistence, based on the analysis of mice deficient for eosinophils [71,72]. More recently, however, alternative explanations have been provided for this observation [73][74][75][76], and a subpopulation of bone marrow stromal cells expressing BAFF has been identified [55], suggesting that BAFF and/or APRIL can be provided by several cell types, including eosinophilic granulocytes, but obviously in a redundant fashion [56].…”