Aryl Hydrocarbon Receptor Activation by Benzo[a]pyrene Prevents Development of Septic Shock and Fatal Outcome in a Mouse Model of Systemic Salmonella enterica Infection
Abstract
:1. Introduction
2. Materials and Methods
2.1. Chemicals and Reagents
2.2. Mice
2.3. Exposure to AhR Ligands In Vivo
2.4. Infection with Salmonella enterica Serovar Enteritidis
2.5. Extra- and Intracellular Bacterial Burden
2.6. Detection of BaP and Its Metabolites in Liver Homogenates by Flow Injection Analysis MS/MS
2.7. Isolation of Microsomes from Murine Liver Tissue and Enzymatic Digestion of BaP
2.8. Characterization of Bacterial Growth Behavior In Vitro
2.9. Peritoneal Lavage
2.10. Incubation of Peritoneal Cavity Cells and Splenocytes with hk S.E.
2.11. Immunophenotyping of Peritoneal Cavity Cells and Splenocytes
2.12. Cytokine Determination in Peritoneal Lavage Fluid, Spleen Cell Culture Supernatants or Sera
2.13. Serum Immunoglobulin Analysis
2.14. Protein Separation and Western Blot
2.15. Determination of Nitric Oxide (NO) Synthesis
2.16. Determination of Phagocytic Activity
2.17. Quantification of mRNA Expression via Real-Time RT-PCR
2.18. Statistical Analysis
3. Results
3.1. BaP Improves the Survival of Mice Infected with S. enteritidis
3.2. Impaired Bactericidal Capacity and Persistent Infection in BaP-Exposed Mice
3.3. Bioavailability of BaP and Its Most Prominent Metabolites in the Liver
3.4. Neither BaP nor BaP Metabolites Affect Survival and Growth Behavior of S.E.
3.5. CD14, MHC Class II and FcγR1 Induction through BaP in Peritoneal Innate Immune Cells
3.6. BaP Alters Functional Properties of Peritoneal Cavity Cells
3.7. S.E.-Specific Antibody Response Is Increased through BaP Exposure
3.8. BaP Alters Cytokine Concentration in Sera
3.9. BaP-Induced Immune Modulation Is Mainly AhR-Dependent
3.10. BaP Activates AhR and Induced Both Canonical and Non-Canonical AhR Signaling Pathways
3.11. mRNA Expression Patterns of Spleen Cells from BaP Exposed C57BL/6 Mice
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Gene | Forward Primer (5′-3′) | Reverse Primer (5′-3′) | UPL Probe |
---|---|---|---|
Ahr | tgcacaaggagtggacga | aggaagctggtctggggtat | 27 |
Ahrr | cagggtaaagagcttcttccaa | ggggaaccctctgtatgagtg | 19 |
Alas1 | ccctccagccaatgagaa | gtgccatctgggactcgt | 40 |
Arnt | tgcctcatctggtactgctg | tgtcctgtggtctgtccagt | 108 |
cJun | ccagaagatggtgtggtgttt | ctgaccctctccccttgc | 11 |
Cyp1a1 Cyp1a2 | tccctccttacagcccaag cctggactgactcccacaac | acgaaggctggaagtccata cgccatctgtaccactgaag | 97 19 |
Foxp3 | agaagctgggagctatgcag | gctacgatgcagcaagagc | 20 |
Gata3 | ttatcaagcccaagcgaag | tggtggtggtctgacagttc | 108 |
G6pdh | ccagcccttcccctatgtat | gtactggaagcccactctcct | 34 |
Ef2 | gtagatgccacccaccactt | gctgcctgtatgccagtgt | 47 |
Gapdh | gagccaaacgggtcatca | catatttctcgtggttcacacc | 29 |
Hprt | tcctcctcagaccgctttt | cctggttcatcatcgctaatc | 95 |
Il1b | ttgacggaccccaaaagat | gaagctggatgctctcatctg | 26 |
Il4 | catcggcattttgaacgag | tctgtggtgttcttcgttgc | 02 |
Il6 | gctaccaaactggatataatcagga | ccaggtagctatggtactccagaa | 06 |
Il10 | gctcctagagctgcggact | tgttgtccagctggtccttt | 41 |
Il12a | atcacaaccatcagcagatca | cgccattatgattcagagactg | 49 |
Il12b | cgcagcaaagcaaggtaagt | cctctagatgcagggagttagc | 103 |
Il17a | gattttcagcaaggaatgtgg | cattgtggagggcagacaat | 34 |
Il18 | catgtacaaagacagtgaagtaagagg | tttcaggtggatccatttcc | 76 |
Il22 | tgacgaccagaacatccaga | cgccttgatctctccactct | 94 |
Il23a | ctgttgccctgggtcact | agcccagtcaggactgctac | 76 |
Ifng | atctggaggaactggcaaaa | ttcaagacttcaaagagtctgaggta | 21 |
iNos | gggctgtcacggagatca | ccatgatggtcacattctgc | 76 |
Nfkb1 | cactgctcaggtccactgtc | ctgtcactatcccggagttca | 69 |
Rela | cccagaccgcagtatccat | gctccaggtctcgcttctt | 47 |
Rorc | acctcttttcacgggagga | tcccacatctcccacattg | 6 |
Tbx21 | tcaaccagcaccagacagag | aaacatcctgtaatggcttgtg | 19 |
Tgfb | tggagcaacatgtggaactc | gtcagcagccggttacca | 72 |
Tnf | tcttctcattcctgcttgtgg | ggtctgggccatagaactga | 49 |
Cell Population | CD11bhigh/F4/80+ | CD11b+/Gr1+ | CD11bhigh/CD11c+ | CD3−/NK1.1+/NKp46+ |
---|---|---|---|---|
Day 1 p.i. | ||||
Vehicle | 4.3 ± 0.5 | 3.4 ± 1.2 | 2.9 ± 0.5 | 0.9 ± 0.1 |
0.02 µg/kg BaP | 3.8 ± 0.3 | 3.3 ± 1.3 | 2.8 ± 0.4 | 1.1 ± 0.1 |
2 µg/kg BaP | 4.9 ± 0.4 | 3.6 ± 1.4 | 2.7 ± 0.6 | 1.1 ± 0.3 |
Day 3 p.i. | ||||
Vehicle | 3.5 ± 0.5 | 11.7 ± 2.9 | 3.4 ± 0.4 | 3.0 ± 0.4 |
0.02 µg/kg BaP | 3.8 ± 0.5 | 12.2 ± 2.9 | 3.4 ± 0.4 | 2.3 ± 0.7 |
2 µg/kg BaP | 3.8 ± 0.4 | 14.0 ± 2.6 | 3.9 ± 1.2 | 2.5 ± 0.4 |
Cell Population | CD11bhigh/F4/80+ | |||
---|---|---|---|---|
Functional marker | MHC-II (I-Ab) | CD64 | CD86 | CD80 |
Day 1 p.i. | ||||
Vehicle | 34,450 ± 2029 | 4230 ± 234 | 2928 ± 232 | 2644 ± 137 |
0.02 µg/kg bw BaP | 48,800 ± 4300 * | 4535 ± 341 | 2602 ± 154 | 2807 ± 112 |
2 µg/kg bw BaP | 40,950 ± 2157 | 5171 ± 278 * | 2883 ± 186 | 3073 ± 219 |
Day 3 p.i. | ||||
Vehicle | 14,025 ± 1202 | 3181 ± 114 | 1620 ± 37 | 1976 ± 112 |
0.02 µg/kg bw BaP | 14,550 ± 639 | 3700 ± 147 * | 1741 ± 43 | 1790 ± 102 |
2 µg/kg bw BaP | 16,233 ± 1876 | 3584 ± 249 | 1670 ± 76 | 1987 ± 85 |
Cell population | CD11b+/Gr-1+ | CD11bhigh/CD11c+ | ||
Functional marker | CD14 | CD64 | MHC-II (I-Ab) | |
Day 1 p.i. | ||||
Vehicle | 5937 ± 812 | 8734 ± 403 | 52,000 ± 2.441 | |
0.02 µg/kg bw BaP | 7097 ± 652 | 9839 ± 990 | 56,600 ± 2.536 | |
2 µg/kg bw BaP | 7956 ± 270 * | 11,028 ± 897 * | 58,420 ± 2.904 | |
Day 3 p.i. | ||||
Vehicle | 2593 ± 377 | 2960 ± 427 | 46,828 ± 1390 | |
0.02 µg/kg bw BaP | 2818 ± 213 | 2890 ± 293 | 51,750 ± 1550 * | |
2 µg/kg bw BaP | 2926 ± 145 | 2761 ± 319 | 50,675 ± 677 * |
Phagocytotic Capacity | ||
---|---|---|
MFI | Positive Cells (%) | |
Vehicle | 27,211 ± 15,613 | 23.57 ± 7.62 |
0.02 µg/kg bw BaP | 52,120 ± 25,018 * | 37.10 ± 7.77 * |
2 µg/kg bw BaP | 35,500 ± 19,465 | 37.83 ± 9.21 * |
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Fueldner, C.; Riemschneider, S.; Haupt, J.; Jungnickel, H.; Schulze, F.; Zoldan, K.; Esser, C.; Hauschildt, S.; Knauer, J.; Luch, A.; et al. Aryl Hydrocarbon Receptor Activation by Benzo[a]pyrene Prevents Development of Septic Shock and Fatal Outcome in a Mouse Model of Systemic Salmonella enterica Infection. Cells 2022, 11, 737. https://doi.org/10.3390/cells11040737
Fueldner C, Riemschneider S, Haupt J, Jungnickel H, Schulze F, Zoldan K, Esser C, Hauschildt S, Knauer J, Luch A, et al. Aryl Hydrocarbon Receptor Activation by Benzo[a]pyrene Prevents Development of Septic Shock and Fatal Outcome in a Mouse Model of Systemic Salmonella enterica Infection. Cells. 2022; 11(4):737. https://doi.org/10.3390/cells11040737
Chicago/Turabian StyleFueldner, Christiane, Sina Riemschneider, Janine Haupt, Harald Jungnickel, Felix Schulze, Katharina Zoldan, Charlotte Esser, Sunna Hauschildt, Jens Knauer, Andreas Luch, and et al. 2022. "Aryl Hydrocarbon Receptor Activation by Benzo[a]pyrene Prevents Development of Septic Shock and Fatal Outcome in a Mouse Model of Systemic Salmonella enterica Infection" Cells 11, no. 4: 737. https://doi.org/10.3390/cells11040737