ZIP8-Mediated Intestinal Dysbiosis Impairs Pulmonary Host Defense against Bacterial Pneumonia
| Autor: | Derrick R. Samuelson, Deandra R. Smith, Kelly C. Cunningham, Todd A. Wyatt, Sannette C. Hall, Daryl J. Murry, Yashpal S. Chhonker, Daren L. Knoell |
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| Rok vydání: | 2022 |
| Předmět: |
DNA
Bacterial zinc transporter QH301-705.5 microbiome zinc pneumonia host defense gut-lung axis DNA Ribosomal Catalysis Inorganic Chemistry Gene Knockout Techniques Mice RNA Ribosomal 16S Animals Biology (General) Physical and Theoretical Chemistry QD1-999 Cation Transport Proteins Lung Molecular Biology Spectroscopy Bacteria Organic Chemistry High-Throughput Nucleotide Sequencing Sequence Analysis DNA General Medicine Pneumonia Pneumococcal Gastrointestinal Microbiome Computer Science Applications Chemistry Disease Models Animal Zinc Streptococcus pneumoniae Dysbiosis Female |
| Zdroj: | International Journal of Molecular Sciences; Volume 23; Issue 3; Pages: 1022 International Journal of Molecular Sciences, Vol 23, Iss 1022, p 1022 (2022) |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms23031022 |
| Popis: | Pneumococcal pneumonia is a leading cause of morbidity and mortality worldwide. An increased susceptibility is due, in part, to compromised immune function. Zinc is required for proper immune function, and an insufficient dietary intake increases the risk of pneumonia. Our group was the first to reveal that the Zn transporter, ZIP8, is required for host defense. Furthermore, the gut microbiota that is essential for lung immunity is adversely impacted by a commonly occurring defective ZIP8 allele in humans. Taken together, we hypothesized that loss of the ZIP8 function would lead to intestinal dysbiosis and impaired host defense against pneumonia. To test this, we utilized a novel myeloid-specific Zip8KO mouse model in our studies. The comparison of the cecal microbial composition of wild-type and Zip8KO mice revealed significant differences in microbial community structure. Most strikingly, upon a S. pneumoniae lung infection, mice recolonized with Zip8KO-derived microbiota exhibited an increase in weight loss, bacterial dissemination, and lung inflammation compared to mice recolonized with WT microbiota. For the first time, we reveal the critical role of myeloid-specific ZIP8 on the maintenance of the gut microbiome structure, and that loss of ZIP8 leads to intestinal dysbiosis and impaired host defense in the lung. Given the high incidence of dietary Zn deficiency and the ZIP8 variant allele in the human population, additional investigation is warranted to improve surveillance and treatment strategies. |
| Databáze: | OpenAIRE |
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