The gut microbiota as a modulator of innate immunity during melioidosis

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 infe...

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Detalles Bibliográficos
Autores principales: Lankelma, Jacqueline M., Birnie, Emma, Weehuizen, Tassili A. F., Scicluna, Brendon P., Belzer, Clara, Houtkooper, Riekelt H., Roelofs, Joris J. T. H., de Vos, Alex F., van der Poll, Tom, Budding, Andries E., Wiersinga, W. Joost
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5411098/
https://www.ncbi.nlm.nih.gov/pubmed/28422970
http://dx.doi.org/10.1371/journal.pntd.0005548
Descripción
Sumario: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.

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