Open AccessThe gut microbiota as a modulator of innate immunity during melioidosis
Author(s) -
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
Publication year - 2017
Publication title -
plos neglected tropical diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.99
H-Index - 135
eISSN - 1935-2735
pISSN - 1935-2727
DOI - 10.1371/journal.pntd.0005548
Subject(s) - melioidosis , biology , burkholderia pseudomallei , microbiology and biotechnology , gut flora , immunology , immunity , inflammation , innate immune system , proteobacteria , sepsis , immune system , bacteria , genetics , 16s ribosomal rna
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.