The gut microbiota as a modulator of innate immunity during melioidosis

PLoS Negl Trop Dis. 2017 Apr 19;11(4):e0005548. doi: 10.1371/journal.pntd.0005548. eCollection 2017 Apr.

Abstract

Background: Melioidosis, caused by the Gram-negative bacterium Burkholderia pseudomallei, is an emerging cause of pneumonia-derived sepsis in the tropics. The gut microbiota supports local mucosal immunity and is increasingly recognized as a protective mediator in host defenses against systemic infection. Here, we aimed to characterize the composition and function of the intestinal microbiota during experimental melioidosis.

Methodology/principal findings: C57BL/6 mice were infected intranasally with B. pseudomallei and sacrificed at different time points to assess bacterial loads and inflammation. In selected experiments, the gut microbiota was disrupted with broad-spectrum antibiotics prior to inoculation. Fecal bacterial composition was analyzed by means of IS-pro, a 16S-23S interspacer region-based profiling method. A marked shift in fecal bacterial composition was seen in all mice during systemic B. pseudomallei infection with a strong increase in Proteobacteria and decrease in Actinobacteria, with an increase in bacterial diversity. We found enhanced early dissemination of B. pseudomallei and systemic inflammation during experimental melioidosis in microbiota-disrupted mice compared with controls. Whole-genome transcriptional profiling of the lung identified several genes that were differentially expressed between mice with a normal or disrupted intestinal microbiota. Genes involved in acute phase signaling, including macrophage-related signaling pathways were significantly elevated in microbiota disrupted mice. Compared with controls, alveolar macrophages derived from antibiotic pretreated mice showed a diminished capacity to phagocytose B. pseudomallei. This might in part explain the observed protective effect of the gut microbiota in the host defense against pneumonia-derived melioidosis.

Conclusions/significance: Taken together, these data identify the gut microbiota as a potential modulator of innate immunity during B. pseudomallei infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / administration & dosage
  • Bacteria / classification*
  • Bacteria / genetics
  • Bacteria / immunology
  • DNA, Ribosomal Spacer / genetics
  • Disease Models, Animal
  • Gastrointestinal Microbiome / immunology*
  • Gastrointestinal Tract / microbiology*
  • Gene Expression Profiling
  • Immunity, Innate*
  • Immunologic Factors / analysis
  • Immunologic Factors / genetics
  • Lung / immunology*
  • Melioidosis / immunology*
  • Mice, Inbred C57BL

Substances

  • Anti-Bacterial Agents
  • DNA, Ribosomal Spacer
  • Immunologic Factors

Grant support

This work was financially supported by the Netherlands Organization for Scientific Research (NWO; VIDI grant to WJW, grant number: 91716475). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.