PLoS Neglected Tropical Diseases (Apr 2017)

The gut microbiota as a modulator of innate immunity during melioidosis.

  • Jacqueline M Lankelma,
  • Emma Birnie,
  • Tassili A F Weehuizen,
  • Brendon P Scicluna,
  • Clara Belzer,
  • Riekelt H Houtkooper,
  • Joris J T H Roelofs,
  • Alex F de Vos,
  • Tom van der Poll,
  • Andries E Budding,
  • W Joost Wiersinga

DOI
https://doi.org/10.1371/journal.pntd.0005548
Journal volume & issue
Vol. 11, no. 4
p. e0005548

Abstract

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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.