Maternal diet modulates the infant microbiome and intestinal Flt3L necessary for dendritic cell development and immunity to respiratory infection

Sikder, Md. Al Amin; Rashid, Ridwan B.; Simpson, Jennifer; Bissell, Alec; Morrison, Mark; Walpole, Carina; Radford, Kristen J.; Kumar, Vinod; Woodruff, Trent M.; Ying, Tan Hui; Ali, Ayesha; Kaiko, Gerard E.; Ahmed, Tufael; Upham, JW; Hoelzle, RD; Cuív, PÓ; Holt, PG; Dennis, PG; Phipps, S; Sebina, Ismail; Howard, Daniel R.; Ullah, Md. Ashik; Rahman, Muhammed Mahfuzur; Lynch, Jason P.; Curren, Bodie; Werder, Rhiannon B.

Title: Maternal diet modulates the infant microbiome and intestinal Flt3L necessary for dendritic cell development and immunity to respiratory infection
Creator: Sikder, Md. Al Amin; Rashid, Ridwan B.; Simpson, Jennifer; Bissell, Alec; Morrison, Mark; Walpole, Carina; Radford, Kristen J.; Kumar, Vinod; Woodruff, Trent M.; Ying, Tan Hui; Ali, Ayesha; Kaiko, Gerard E.; Ahmed, Tufael; Upham, JW; Hoelzle, RD; Cuív, PÓ; Holt, PG; Dennis, PG; Phipps, S; Sebina, Ismail; Howard, Daniel R.; Ullah, Md. Ashik; Rahman, Muhammed Mahfuzur; Lynch, Jason P.; Curren, Bodie; Werder, Rhiannon B.
Relation: Immunity Vol. 56, Issue 5, p. 1098-1114.e10
Publisher Link: http://dx.doi.org/10.1016/j.immuni.2023.03.002
Publisher: Cell Press
Resource Type: journal article
Date: 2023
Description: Poor maternal diet during pregnancy is a risk factor for severe lower respiratory infections (sLRIs) in the offspring, but the underlying mechanisms remain elusive. Here, we demonstrate that in mice a maternal low-fiber diet (LFD) led to enhanced LRI severity in infants because of delayed plasmacytoid dendritic cell (pDC) recruitment and perturbation of regulatory T cell expansion in the lungs. LFD altered the composition of the maternal milk microbiome and assembling infant gut microbiome. These microbial changes reduced the secretion of the DC growth factor Flt3L by neonatal intestinal epithelial cells and impaired downstream pDC hematopoiesis. Therapy with a propionate-producing bacteria isolated from the milk of high-fiber diet-fed mothers, or supplementation with propionate, conferred protection against sLRI by restoring gut Flt3L expression and pDC hematopoiesis. Our findings identify a microbiome-dependent Flt3L axis in the gut that promotes pDC hematopoiesis in early life and confers disease resistance against sLRIs.
Subject: dendritic cells; bronchiolitis; asthma; regulatory T cell; microbiome; acute lower respiratory tract infection; SDG 3; Sustainable Development Goals
Identifier: http://hdl.handle.net/1959.13/1494045
Identifier: uon:53688
Identifier: ISSN:1074-7613
Language: eng
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