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Commensal Propionibacterium strain UF1 mitigates intestinal inflammation via Th17 cell regulation
Natacha Colliou, … , Shuzhao Li, Mansour Mohamadzadeh
Natacha Colliou, … , Shuzhao Li, Mansour Mohamadzadeh
Published September 25, 2017
Citation Information: J Clin Invest. 2017;127(11):3970-3986. https://doi.org/10.1172/JCI95376.
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Research Article Immunology Inflammation Article has an altmetric score of 19

Commensal Propionibacterium strain UF1 mitigates intestinal inflammation via Th17 cell regulation

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Abstract

Consumption of human breast milk (HBM) attenuates the incidence of necrotizing enterocolitis (NEC), which remains a leading and intractable cause of mortality in preterm infants. Here, we report that this diminution correlates with alterations in the gut microbiota, particularly enrichment of Propionibacterium species. Transfaunation of microbiota from HBM-fed preterm infants or a newly identified and cultured Propionibacterium strain, P. UF1, to germfree mice conferred protection against pathogen infection and correlated with profound increases in intestinal Th17 cells. The induction of Th17 cells was dependent on bacterial dihydrolipoamide acetyltransferase (DlaT), a major protein expressed on the P. UF1 surface layer (S-layer). Binding of P. UF1 to its cognate receptor, SIGNR1, on dendritic cells resulted in the regulation of intestinal phagocytes. Importantly, transfer of P. UF1 profoundly mitigated induced NEC-like injury in neonatal mice. Together, these results mechanistically elucidate the protective effects of HBM and P. UF1–induced immunoregulation, which safeguard against proinflammatory diseases, including NEC.

Authors

Natacha Colliou, Yong Ge, Bikash Sahay, Minghao Gong, Mojgan Zadeh, Jennifer L. Owen, Josef Neu, William G. Farmerie, Francis Alonzo III, Ken Liu, Dean P. Jones, Shuzhao Li, Mansour Mohamadzadeh

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Figure 9

Mitigation of NEC-like injury by P. UF1 in newborn mice.

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Mitigation of NEC-like injury by P. UF1 in newborn mice.
(A) C57BL/6 pre...
(A) C57BL/6 pregnant dams were gavaged with P. UF1 or PBS twice/week during gestation. Five days after birth, newborn mice were sacrificed. Representative data of flow plots, percentages, and total cell counts of Th17 cells and IL-10+TGF-β+ Tregs in newborn mice. Each dot represents 3 pooled small intestinal tissues from each group of newborn mice. (B and C) Five days after birth, newborn mice of dams gavaged with P. UF1 or PBS were separated and subjected to NEC-like injury. Newborn mice gavaged with PBS or P. UF1 (107 CFU/mouse) on days 1, 3, and 5. Newborn mice were sacrificed 6 days later. Survival curve and weight incidence of the newborn mice subjected to NEC-like injury (B), and representative H&E sections of the small intestine of control newborn mice (PBS) or mice subjected to NEC-like injury with or without P. UF1. (C) Original magnification, ×10. (D) qRT-PCR demonstrating expression of proinflammatory genes in the small intestine of P. UF1–gavaged or untreated newborn mice subjected to NEC-like injury. Control newborn mice (PBS) with no NEC-like injury. (E and F) Representative data of flow plots, percentages, and total cell counts of IL-1β+, IL-6+, IL-12/23p40+, IL-10+, and TGF-β+ DCs (E), IL-10+ Th17 cells, and IL-10+ TGF-β+ Tregs (F) in the indicated groups. Data are pooled from 3 experiments in steady state (n = 15 newborn mice/group, A) and for NEC-like injury (PBS, n = 10 newborn mice; NEC, n = 12 newborn mice; NEC + P. UF1, n = 17 newborn mice, E) or 4 experiments (NEC, n = 33 newborn mice; NEC + P. UF1, n = 30 newborn mice, B). Error bars represent mean ± SEM. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001, 2-tailed unpaired t test (A and B) or Kruskal-Wallis test (D–F).

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ISSN: 0021-9738 (print), 1558-8238 (online)

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