Journal
OPEN FORUM INFECTIOUS DISEASES
Volume 8, Issue 6, Pages -Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/ofid/ofab237
Keywords
diarrhea; pneumonia; innate immunity; neutrophils; NETs
Categories
Funding
- Department of Defense [W81XWH-17-1-0109]
- National Institutes of Health [R01HD093826, R01AI130378]
- National Cancer Institute [5P30CA042014-24]
- University of Utah Flow Cytometry Facility
- CMC animal facility
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The study found that intestinal infection impacts lung innate immune responses, especially neutrophil characteristics, potentially increasing susceptibility to secondary pneumonia. Mice with prior intestinal infection had higher lung bacterial burden and inflammation when challenged with Klebsiella pneumoniae.
Background Pneumonia and diarrhea are among the leading causes of death worldwide, and epidemiological studies have demonstrated that diarrhea is associated with an increased risk of subsequent pneumonia. Our aim was to determine the impact of intestinal infection on innate immune responses in the lung. Methods Using a mouse model of intestinal infection by Salmonella enterica serovar Typhimurium (S. Typhimurium [ST]), we investigated associations between gastrointestinal infections and lung innate immune responses to bacterial (Klebsiella pneumoniae) challenge. Results We found alterations in frequencies of innate immune cells in the lungs of intestinally infected mice compared with uninfected mice. On subsequent challenge with K. pneumoniae, we found that mice with prior intestinal infection have higher lung bacterial burden and inflammation, increased neutrophil margination, and neutrophil extracellular traps, but lower overall numbers of neutrophils, compared with mice without prior intestinal infection. Total numbers of dendritic cells, innate-like T cells, and natural killer cells were not different between mice with and without prior intestinal infection. Conclusions Together, these results suggest that intestinal infection impacts lung innate immune responses, most notably neutrophil characteristics, potentially resulting in increased susceptibility to secondary pneumonia.
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