Regulation of splenic monocyte homeostasis and function by gut microbial products

Panayota Kolypetri; Shirong Liu; Laura M Cox; Mai Fujiwara; Radhika Raheja; Dvora Ghitza; Anya Song; Dominique Daatselaar; Valerie Willocq; Howard L Weiner

doi:10.1016/j.isci.2021.102356

Regulation of splenic monocyte homeostasis and function by gut microbial products

iScience. 2021 Mar 25;24(4):102356. doi: 10.1016/j.isci.2021.102356. eCollection 2021 Apr 23.

Authors

Panayota Kolypetri^{1

2}, Shirong Liu^{1

2}, Laura M Cox^{1

2}, Mai Fujiwara^{1

2}, Radhika Raheja^{1

2}, Dvora Ghitza^{1

2}, Anya Song^{1

2}, Dominique Daatselaar^{1

2}, Valerie Willocq^{1

2}, Howard L Weiner^{1

2}

Affiliations

¹ Department of Neurology, Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
² Evergrande Center for Immunologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.

Abstract

Splenic Ly6C^high monocytes are innate immune cells involved in the regulation of central nervous system-related diseases. Recent studies have reported the shaping of peripheral immune responses by the gut microbiome via mostly unexplored pathways. In this study, we report that a 4-day antibiotic treatment eliminates certain families of the Bacteroidetes, Firmicutes, Tenericutes, and Actinobacteria phyla in the gut and reduces the levels of multiple pattern recognition receptor (PRR) ligands in the serum. Reduction of PRR ligands was associated with reduced numbers and perturbed function of splenic Ly6C^high monocytes, which acquired an immature phenotype producing decreased levels of inflammatory cytokines and exhibiting increased phagocytic and anti-microbial abilities. Addition of PRR ligands in antibiotic-treated mice restored the number and functions of splenic Ly6C^high monocytes. Our data identify circulating PRR ligands as critical regulators of the splenic Ly6C^high monocyte behavior and suggest possible intervention pathways to manipulate this crucial immune cell subset.

Keywords: Immunology; Microbiology; Microbiome.