TY - JOUR
T1 - The gut microbiota as a modulator of innate immunity during melioidosis
AU - Lankelma, Jacqueline M.
AU - Birnie, Emma
AU - Weehuizen, Tassili A.F.
AU - Scicluna, Brendon P.
AU - Belzer, Clara
AU - Houtkooper, Riekelt H.
AU - Roelofs, Joris J.T.H.
AU - de Vos, Alex F.
AU - van der Poll, Tom
AU - Budding, Andries E.
AU - Wiersinga, W. Joost
PY - 2017/4/19
Y1 - 2017/4/19
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85019028651&partnerID=8YFLogxK
U2 - https://doi.org/10.1371/journal.pntd.0005548
DO - https://doi.org/10.1371/journal.pntd.0005548
M3 - Article
C2 - 28422970
SN - 1935-2727
VL - 11
SP - e0005548
JO - PLoS neglected tropical diseases
JF - PLoS neglected tropical diseases
IS - 4
M1 - e0005548
ER -