Aged mice display altered numbers and phenotype of basophils, and bone marrow-derived basophil activation, with a limited role for aging-associated microbiota

Adriaan A van Beek; Floris Fransen; Ben Meijer; Paul de Vos; Edward F Knol; Huub F J Savelkoul

doi:10.1186/s12979-018-0135-6

Aged mice display altered numbers and phenotype of basophils, and bone marrow-derived basophil activation, with a limited role for aging-associated microbiota

Immun Ageing. 2018 Nov 29:15:32. doi: 10.1186/s12979-018-0135-6. eCollection 2018.

Authors

Adriaan A van Beek^{1

2

3}, Floris Fransen^{2

4}, Ben Meijer¹, Paul de Vos^{2

4}, Edward F Knol^{5

6}, Huub F J Savelkoul¹

Affiliations

¹ 1Cell Biology and Immunology Group, Wageningen University, Wageningen, the Netherlands.
² 2Top Institute Food and Nutrition, Wageningen, the Netherlands.
³ 3Department of Immunology, Erasmus University Medical Center, Dr. Molewaterplein 40, 3015 GD Rotterdam, the Netherlands.
⁴ 4Pathology and Medical Biology, University of Groningen, Groningen, the Netherlands.
⁵ 5Department of Immunology, University Medical Center, Utrecht, the Netherlands.
⁶ 6Dermatology/Allergology, University Medical Center, Utrecht, the Netherlands.

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 4-month-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 aging-associated 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; Bone marrow; Immunity; Microbiota; Spleen.