The Gut Microbiome Modulates the Functionality of CD71+ Erythroid Cells in the Newborn

• Author / Creator

  Bahojb Habibyan, Yasaman

• Mounting preclinical and clinical evidence strongly supports the crucial role of the gut microbiota in health. A dysbiosis of the microbiome, an imbalance of the microbial populations, may predispose newborns to develop various immune disorders later in life, such as Inflammatory Bowel Disease (IBD) and Type 1 Diabetes (T1D). Thus, it is fundamental to investigate the mechanism by which the immune system can tolerate and coexist with the microbiome. It has been shown that CD71+ erythroid cells (CECs) are abundant in newborns relative to adults. The removal of CECs from the intestinal tissues by the anti-CD71 antibody disrupts immune homeostasis and results in inflammation. This suggests an essential role for CECs in the adaptation of newborns to colonization with microbial communities.
  
  Therefore, I sought to characterize CD45- and CD45+ CECs in the gut and spleen of newborn mice. I looked at the expression of V-domain immunoglobulin suppressor of T cell activation (VISTA), transforming growth factor-beta (TGF-), reactive oxygen species (ROS), and arginase-1. I found that CD45+ CECs in newborns had higher expression of all measured immune factors relative to CD45- CECs in both the gut and the spleen. I next sought to characterize CD45- and CD45+ CECs in SPF and GF mice. I found that CD45- and CD45+ CECs from germ-free (GF) mice significantly lower the expression of immune mediators relative to specific-pathogen-free (SPF) mice. I next assessed the expression of toll-like receptors (TLRs) by CECs in SPF mice. I found that CD45+ CECs had significantly higher expression of TLRs relative to CD45- CECs. These findings indicate that CECs, specifically the CD45+ CECs are capable of microbial sensing and differ phenotypically in the absence of the microbiome. Finally, I explored whether a single depletion of CD71 on day 3 was sufficient to cause long-term microbial dysbiosis by either day 22 or day 36. I found that a single early depletion of CD71 did not result in long-term microbial dysbiosis by day 22. However, interestingly, by day 36 I found significant differences in beta diversity. These preliminary findings indicate that there is an interaction between CECs and the microbiome in early life. These results may be combined with ongoing research to potentially identify a novel and critical role for CECs in immune tolerance and microbial dysbiosis.

• Subjects / Keywords

  • microbiome
  • erythroid

• Graduation date

  Spring 2023

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/r3-at9d-7h63

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.