Maternal high-fat diet results in microbiota-dependent expansion of ILC3s in mice offspring
Sarah Thomas Babu, Xinying Niu, Megan Raetz, Rashmin C. Savani, Lora V. Hooper, Julie Mirpuri
Sarah Thomas Babu, Xinying Niu, Megan Raetz, Rashmin C. Savani, Lora V. Hooper, Julie Mirpuri
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Research Article Immunology Inflammation

Maternal high-fat diet results in microbiota-dependent expansion of ILC3s in mice offspring

Abstract

Maternal obesity and a high-fat diet (HFD) during the perinatal period have documented short- and long-term adverse outcomes for offspring. However, the mechanisms of maternal HFD effects on neonatal offspring are unclear. While the effects of maternal HFD exposure during pregnancy on the offspring are increasingly being appreciated, we do not know if maternal HFD alters the microbiota or affects neonatal susceptibility to inflammatory conditions, nor the mechanisms involved. In this study, we show that the offspring of mothers exposed to HFD develop a unique microbiota, marked by expansion of Firmicutes, and an increase in IL-17–producing type 3 innate lymphoid cells (ILC3s). The expansion of ILC3s was recapitulated through neocolonization with HFD microbiota alone. Further, the HFD offspring were susceptible to a neonatal model of inflammation that was reversible with IL-17 blockade. Collectively, these data suggest a previously unknown and unique role for ILC3s in the promotion of an early inflammatory susceptibility in the offspring of mothers exposed to HFD.

Authors

Sarah Thomas Babu, Xinying Niu, Megan Raetz, Rashmin C. Savani, Lora V. Hooper, Julie Mirpuri

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Figure 3

Rag1–/– mice on HFD have an expanded population of IL-17–producing ILC3s.

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Rag1–/– mice on HFD have an expanded population of IL-17–producing ILC3...
(A) Flow cytometric analysis of lamina propria (LP) cells from 2-week-old RD Rag1–/– and HFD Rag1–/– offspring was performed. Live cells were stained for CD45 (x axis) and IL-17 (y axis) and representative panels are shown here. Cells positive for CD45 and IL-17 are highlighted in the bold boxes. (B) Percentage of CD45+IL-17+ cells (left) and percentage of IL-17+Rorγt+CD4–CD127+NKp46+CD117+ ILC3s (right) in 2-week-old RD Rag1–/– and HFD Rag1–/– offspring. (C) Quantification of Firmicutes (log scale) in the small intestine of 2-week-old RD Rag1–/–and HFD Rag1–/– offspring by qRT-PCR. (D) Flow cytometric analysis of LP cells from 2-week-old neocolonized RD and neocolonized HFD offspring was performed. Cells positive for CD45 and IL-17 are highlighted in the bold boxes. (E) Percentage of IL-17+ cells and IL-17–producing ILC3s in 2-week-old neocolonized offspring. (F) Quantification of Firmicutes (log scale) in the small intestine of 2-week-old neocolonized RD and neocolonized HFD offspring by qRT-PCR. The data shown are representative of 3 experiments with 7–10 mice in each group, and are depicted as the mean ± SEM. *P < 0.05; **P < 0.01 by 2-tailed Student’s t test. HFD, high-fat diet; RD, regular diet.