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

Md Al Amin Sikder¹, Ridwan B Rashid², Tufael Ahmed³, Ismail Sebina⁴, Daniel R Howard², Md Ashik Ullah⁴, Muhammed Mahfuzur Rahman², Jason P Lynch⁴, Bodie Curren⁴, Rhiannon B Werder⁴, Jennifer Simpson⁵, Alec Bissell⁴, Mark Morrison⁶, Carina Walpole⁷, Kristen J Radford⁷, Vinod Kumar⁸, Trent M Woodruff⁹, Tan Hui Ying¹⁰, Ayesha Ali¹⁰, Gerard E Kaiko¹⁰, John W Upham¹¹, Robert D Hoelzle¹², Páraic Ó Cuív¹³, Patrick G Holt¹⁴, Paul G Dennis¹⁵, Simon Phipps¹⁶

Affiliations

¹ QIMR Berghofer Medical Research Institute, Herston, Brisbane, QLD 4006, Australia; School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane, QLD 4072, Australia; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Dhaka, Dhaka 1000, Bangladesh.
² QIMR Berghofer Medical Research Institute, Herston, Brisbane, QLD 4006, Australia; School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane, QLD 4072, Australia.
³ QIMR Berghofer Medical Research Institute, Herston, Brisbane, QLD 4006, Australia; School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD 4000, Australia.
⁴ QIMR Berghofer Medical Research Institute, Herston, Brisbane, QLD 4006, Australia.
⁵ QIMR Berghofer Medical Research Institute, Herston, Brisbane, QLD 4006, Australia; School of Biomedical Sciences and Pharmacy, Faculty of Health, University of Newcastle, Newcastle, NSW, Australia.
⁶ University of Queensland Frazer Institute, Faculty of Medicine, The University of Queensland, Woolloongabba, Brisbane, QLD 4102, Australia; Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, QLD, Australia.
⁷ Mater Research Institute, The University of Queensland, Translational Research Institute, Wolloongabba, Brisbane, QLD 4102, Australia.
⁸ School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane, QLD 4072, Australia.
⁹ School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane, QLD 4072, Australia; Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, QLD, Australia.
¹⁰ School of Biomedical Sciences and Pharmacy, Faculty of Health, University of Newcastle, Newcastle, NSW, Australia; Hunter Medical Research Institute, Newcastle, NSW, Australia.
¹¹ University of Queensland Frazer Institute, Faculty of Medicine, The University of Queensland, Woolloongabba, Brisbane, QLD 4102, Australia; Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, QLD, Australia; Princess Alexandra Hospital, Brisbane, QLD, Australia.
¹² The School of Earth and Environmental Sciences, The University of Queensland, Brisbane, QLD 4072, Australia.
¹³ Mater Research Institute, The University of Queensland, Translational Research Institute, Wolloongabba, Brisbane, QLD 4102, Australia; Microba Life Sciences, Translational Research Institute, Woolloongabba, Brisbane, QLD 4102, Australia.
¹⁴ Telethon Kids Institute, The University of Western Australia, Nedlands, WA 6009, Australia.
¹⁵ Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, QLD, Australia; The School of Earth and Environmental Sciences, The University of Queensland, Brisbane, QLD 4072, Australia.
¹⁶ QIMR Berghofer Medical Research Institute, Herston, Brisbane, QLD 4006, Australia; School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane, QLD 4072, Australia; School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD 4000, Australia; Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, QLD, Australia. Electronic address: simon.phipps@qimrberghofer.edu.au.

PMID: 37003256
DOI: 10.1016/j.immuni.2023.03.002

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

Md Al Amin Sikder et al. Immunity. 2023.

. 2023 May 9;56(5):1098-1114.e10.

doi: 10.1016/j.immuni.2023.03.002. Epub 2023 Mar 31.

Authors

Affiliations

¹ QIMR Berghofer Medical Research Institute, Herston, Brisbane, QLD 4006, Australia; School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane, QLD 4072, Australia; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Dhaka, Dhaka 1000, Bangladesh.
² QIMR Berghofer Medical Research Institute, Herston, Brisbane, QLD 4006, Australia; School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane, QLD 4072, Australia.
³ QIMR Berghofer Medical Research Institute, Herston, Brisbane, QLD 4006, Australia; School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD 4000, Australia.
⁴ QIMR Berghofer Medical Research Institute, Herston, Brisbane, QLD 4006, Australia.
⁵ QIMR Berghofer Medical Research Institute, Herston, Brisbane, QLD 4006, Australia; School of Biomedical Sciences and Pharmacy, Faculty of Health, University of Newcastle, Newcastle, NSW, Australia.
⁶ University of Queensland Frazer Institute, Faculty of Medicine, The University of Queensland, Woolloongabba, Brisbane, QLD 4102, Australia; Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, QLD, Australia.
⁷ Mater Research Institute, The University of Queensland, Translational Research Institute, Wolloongabba, Brisbane, QLD 4102, Australia.
⁸ School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane, QLD 4072, Australia.
⁹ School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane, QLD 4072, Australia; Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, QLD, Australia.
¹⁰ School of Biomedical Sciences and Pharmacy, Faculty of Health, University of Newcastle, Newcastle, NSW, Australia; Hunter Medical Research Institute, Newcastle, NSW, Australia.
¹¹ University of Queensland Frazer Institute, Faculty of Medicine, The University of Queensland, Woolloongabba, Brisbane, QLD 4102, Australia; Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, QLD, Australia; Princess Alexandra Hospital, Brisbane, QLD, Australia.
¹² The School of Earth and Environmental Sciences, The University of Queensland, Brisbane, QLD 4072, Australia.
¹³ Mater Research Institute, The University of Queensland, Translational Research Institute, Wolloongabba, Brisbane, QLD 4102, Australia; Microba Life Sciences, Translational Research Institute, Woolloongabba, Brisbane, QLD 4102, Australia.
¹⁴ Telethon Kids Institute, The University of Western Australia, Nedlands, WA 6009, Australia.
¹⁵ Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, QLD, Australia; The School of Earth and Environmental Sciences, The University of Queensland, Brisbane, QLD 4072, Australia.
¹⁶ QIMR Berghofer Medical Research Institute, Herston, Brisbane, QLD 4006, Australia; School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane, QLD 4072, Australia; School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD 4000, Australia; Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, QLD, Australia. Electronic address: simon.phipps@qimrberghofer.edu.au.

PMID: 37003256
DOI: 10.1016/j.immuni.2023.03.002

Abstract

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.

Keywords: Flt3L; acute lower respiratory tract infection; asthma; bronchiolitis; dendritic cells; microbiome; milk; regulatory T cell; respiratory synctial virus; virus.

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Conflict of interest statement

Declaration of interests The authors declare no competing interests.

Comment in

Propionate primes the DC pump in neonates.
Rice TA, Konnikova L. Rice TA, et al. Immunity. 2023 May 9;56(5):903-905. doi: 10.1016/j.immuni.2023.04.006. Immunity. 2023. PMID: 37163990

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

Affiliations

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

Authors

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Abstract

Conflict of interest statement

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