4.5 Article

Toll-like receptors, environmental caging, and lung dysbiosis

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AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajplung.00002.2021

关键词

cage; lung microbiome; toll-like receptors

资金

  1. NIH National Heart, Lung, and Blood Institute [R00HL139996, R35HL144481, R01HL121774]
  2. National Institute of Allergy and Infectious Diseases [R01AI138348]

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The absence of toll-like receptors results in altered lung microbiota with changes in community composition, reduced diversity, and bacterial burden. Co-housing wild-type mice with toll-like receptor-deficient mice for 3 weeks did not significantly affect the composition of the lung microbiome. Toll-like receptor signaling plays a role in shaping lung microbiota.
Recent studies have implicated lung microbiota in shaping local alveolar immune responses. Toll-like receptors are major sensors of microbiota and determinants of local epithelial homeostasis. The impact of toll-like receptor deficiency on lung microbiota is unknown. To determine whether the absence of toll-like receptors results in altered lung microbiota or dysbiosis, we compared lung microbiota in wild-type and toll-like receptor-deficient experimental mice using 16S ribosomal RNA gene quantification and sequencing. We used a randomized environmental caging strategy to determine the impact of toll-like receptors on lung microbiota. Lung microbiota are detectable in toll-like receptor-deficient experimental mice and exhibit considerable variability. The lung microbiota of toll-like receptor-deficient mice are altered in community composition (PERMANOVA P < 0.001), display reduced diversity (t test P = 0.0075), and bacterial burden (t test P = 0.016) compared with wild-type mice with intact tolllike receptors and associated signaling pathways. The lung microbiota of wild-type mice when randomized to cages with toll-like receptor-deficient mice converged with no significant difference in community composition (PERMANOVA P > 0.05) after 3 wk of cohousing. The lung microbiome of toll-like receptor-deficient mice is distinct from wild-type mice and may be less susceptible to the effects of caging as an environmental variable. Our observations support a role for toll-like receptor signaling in the shaping of lung microbiota.

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