Candidate genes on murine chromosome 8 are associated with susceptibility to Staphylococcus aureus infection in mice and are involved with Staphylococcus aureus septicemia in humans
| Autor: | Sun Hee Ahn, Felix Mba Medie, Carlton Adams, Robert Qi, Qin Yan, William K. Scott, Hitesh Deshmukh, Batu K. Sharma-Kuinkel, Christopher W. Woods, Brenda Hansen, Chen Hsin Albert Yu, Lawrence P. Park, Ephraim L. Tsalik, Vance G. Fowler, Derek D. Cyr |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Candidate gene Neutrophils Microarrays Staphylococcus lcsh:Medicine Apoptosis Cell Cycle Proteins medicine.disease_cause Ligands Pathology and Laboratory Medicine Biochemistry White Blood Cells Bone Marrow Animal Cells Gene expression Medicine and Health Sciences Small interfering RNAs Staphylococcus Aureus RNA Small Interfering lcsh:Science Multidisciplinary Cell Death Chromosome Biology Chromosome Mapping Nuclear Proteins Staphylococcal Infections 3. Good health Bacterial Pathogens Nucleic acids Bioassays and Physiological Analysis Staphylococcus aureus Medical Microbiology Cell Processes Pathogens Cellular Types Research Article Immune Cells Quantitative Trait Loci Immunology Locus (genetics) Biology Quantitative trait locus Genetic Predisposition Research and Analysis Methods Polymorphism Single Nucleotide Microbiology Chromosomes 03 medical and health sciences Antigen Antigens CD Sepsis medicine Genetics Animals Humans Genetic Predisposition to Disease Non-coding RNA Gene Microbial Pathogens Alleles Genetic Association Studies Blood Cells Bacteria Chromosome 8 Macrophages lcsh:R Organisms Chromosome Reproducibility of Results Biology and Life Sciences Cell Biology Chromosome Pairs Chromosomes Mammalian Gene regulation Mice Inbred C57BL 030104 developmental biology Gene Expression Regulation Genetics of Disease RNA lcsh:Q |
| Zdroj: | PLoS ONE PLoS ONE, Vol 12, Iss 6, p e0179033 (2017) |
| ISSN: | 1932-6203 |
| Popis: | We previously showed that chromosome 8 of A/J mice was associated with susceptibility to S. aureus infection. However, the specific genes responsible for this susceptibility are unknown. Chromosome substitution strain 8 (CSS8) mice, which have chromosome 8 from A/J but an otherwise C57BL/6J genome, were used to identify the genetic determinants of susceptibility to S. aureus on chromosome 8. Quantitative trait loci (QTL) mapping of S. aureus-infected N2 backcross mice (F1 [C8A] × C57BL/6J) identified a locus 83180780-88103009 (GRCm38/mm10) on A/J chromosome 8 that was linked to S. aureus susceptibility. All genes on the QTL (n~ 102) were further analyzed by three different strategies: 1) different expression in susceptible (A/J) and resistant (C57BL/6J) mice only in response to S. aureus, 2) consistently different expression in both uninfected and infected states between the two strains, and 3) damaging non-synonymous SNPs in either strain. Eleven candidate genes from the QTL region were significantly differently expressed in patients with S. aureus infection vs healthy human subjects. Four of these 11 genes also exhibited significantly different expression in S. aureus-challenged human neutrophils: Ier2, Crif1, Cd97 and Lyl1. CD97 ligand binding was evaluated within peritoneal neutrophils from A/J and C57BL/6J. CD97 from A/J had stronger CD55 but weaker integrin α5β1 ligand binding as compared with C57BL/6J. Because CD55/CD97 binding regulates immune cell activation and cytokine production, and integrin α5β1 is a membrane receptor for fibronectin, which is also bound by S. aureus, strain-specific differences could contribute to susceptibility to S. aureus. Down-regulation of Crif1 with siRNA was associated with increased host cell apoptosis among both naïve and S. aureus-infected bone marrow-derived macrophages. Specific genes in A/J chromosome 8, including Cd97 and Crif1, may play important roles in host defense against S. aureus. |
| Databáze: | OpenAIRE |
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