Aged mice display altered numbers and phenotype of basophils, and bone marrow-derived basophil activation, with a limite
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RESEARCH
Open Access
Aged mice display altered numbers and phenotype of basophils, and bone marrowderived basophil activation, with a limited role for aging-associated microbiota Adriaan A. van Beek1,2,3*, Floris Fransen2,4, Ben Meijer1, Paul de Vos2,4, Edward F. Knol5,6 and Huub F. J. Savelkoul1
Abstract Background: The influence of age on basophils is poorly understood, as well as the effect of aging-associated microbiota on basophils. Therefore, we studied the influence of aging and aging-associated microbiota on basophil frequency and phenotype, and differentiation from basophil precursors. Results: Basophils became more abundant in bone marrow (BM) and spleens of 19-month-old mice compared with 4month-old mice. Aged basophils tended to express less CD200R3 and more CD123, both in BM and spleen. Differences in microbiota composition with aging were confirmed by 16S sequencing. Microbiota transfers from young and old mice to germ-free recipients revealed that CD11b tended to be lowered on splenic basophils by agingassociated microbiota. Furthermore, abundance of Alistipes, Oscillibacter, Bacteroidetes RC9 gut group, and S24– 7 family positively correlated and CD123 expression, whereas Akkermansia abundance negatively correlated with basophils numbers. Subsequently, we purified FcεRIα+CD11c−CD117− BM-derived basophils and found that those from aged mice expressed lower levels of CD11b upon stimulation. Higher frequencies of IL-4+ basophils were generated from basophil precursors of aged mice, which could be reproduced in basophils derived from germ-free recipients of aging-associated microbiota. Conclusions: Collectively, these results show the influence of aging on basophils. Furthermore, this study shows that aging-associated microbiota altered activation of BM-derived basophils in a similar fashion as observed in BM-derived basophils from aged mice. Keywords: Aging, Basophils, Immunity, Microbiota, Bone marrow, Spleen
Background The human adult gut contains about 1013–1014 bacteria [1, 2], which is comparable to the number of human cells in the total body of a 30-year-old adult [3]. These commensal gut microbiota modulate the immune system [4] and contribute to immune homeostasis in the mucosal immune system [5]. Gut microbiota play an important modulatory role beyond mucosal immunity, for instance by changing the stem cell niche in the bone * Correspondence: [email protected] 1 Cell Biology and Immunology Group, Wageningen University, Wageningen, the Netherlands 2 Top Institute Food and Nutrition, Wageningen, the Netherlands Full list of author information is available at the end of the article
marrow (BM) [6]. Furthermore, absence of microbe-derived peptidoglycan in the circulation impairs the killing by BM neutrophils of Salmonella pneumoniae and Staphylococcus aureus [7]. In addition, in the absence of microbiota, CD123 (IL-3Rα) expression on basophil precursors was upregulated, thereby enhancing their responsiveness to interleukin (IL) 3 [8]. During aging the immune system develops several defec
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