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

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Article numbere0005548
JournalPLoS Neglected Tropical Diseases
Volume11
Issue number4
DOIs
Publication statusPublished - 19 Apr 2017

Cite this

Lankelma, J. M., Birnie, E., Weehuizen, T. A. F., Scicluna, B. P., Belzer, C., Houtkooper, R. H., ... Wiersinga, W. J. (2017). The gut microbiota as a modulator of innate immunity during melioidosis. PLoS Neglected Tropical Diseases, 11(4), [e0005548]. https://doi.org/10.1371/journal.pntd.0005548