NSG-Mice Reveal the Importance of a Functional Innate and Adaptive Immune Response to Overcome RVFV Infection
Abstract
:1. Introduction
2. Materials and Methods
2.1. Virus
2.2. Mice
2.3. Infection and Study Design
2.4. RNA Isolation and Reverse Transcription Quantitative Polymerase Chain Reaction
2.5. Serum Neutralization Test
2.6. Histology and Immunohistochemistry
2.7. Statistical Analysis
3. Results
3.1. Survival and Clinical Signs
3.2. Reverse Transcription Quantitative Polymerase Chain Reaction
3.3. Serum Neutralization Test
3.4. Histology and Immunohistochemistry
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Disclaimer
References
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No. | Designation | Immunological Trait | Number of Infected/Placebo Animals | Origin | References |
---|---|---|---|---|---|
1 | B6-IFNARtmAgt | No IFNAR expression | 6/6 | FLI | [50] |
2 | C.129S7(B6)-Ifngtm1/s/J | Impaired Interferon γ response and therefore decreased activity of macrophage function | 12/6 | FLI | [51] |
3 | B6-TLR3tm1Flv | TLR 3 deficiency | 12/6 | FLI | [52] |
4 | B6-TLR7tm1Aki | TLR 7 deficiency | 12/6 | FLI | [52] |
5 | B6-CD4tm1Mak | Block of CD4+ T-Lymphocyte development and restricted T-helper-cell response | 6/6 | FLI | [53] |
6 | B6-CD8atm1Mak | Deficient in functional cytotoxic T-Lymphocytes | 6/6 | FLI | [54] |
7 | Foxn1nu-/- (NUDE) | Lack of thymus and therefore absence of T-Lymphocytes, partial defect in B-cell development | 6/6 | JAX | [55] |
8 | Igh-Jtm1DhuN?+N2 | No B-cell maturation, therefore no IgM or IgG production | 6/6 | TAC | [56] |
9 | NOD.Cg-Prkdcscid Il2rgtm1WjI/SzJ (NSG) | No lymphocyte maturation (B and T cells), therefore no IgG and extremely low cytotoxic T-cells, deficiency of NK cells, macrophages and dendritic cells, absence of complement C5 | 12/6 | CRL | [54,56,57,58,59] |
10 | C57Bl/6 | Wildtype, background of strain 1, 3-6 | 9/6 | FLI | [20] |
11 | BALB/c | Wildtype, background of strain 2 and 8 | 12/6 | FLI | [20] |
12 | Foxn1nu+/- (NUDE heterozygous) | Heterozygous control for strain 7 | 6/6 | JAX | [55] |
13 | NOD/ShiLtJ (NOD) | Background of strain 9 (NSG), late-onset spontaneous Autoimmune diabetes mellitus, deficient NK cells, macrophages, dendritic cells and complement component C5 | 12/6 | CRL | [56,58,59,60] |
Category | Description of Signs | Score |
---|---|---|
Posture and appearance | Normal posture, smooth fur | 0 |
Normal posture, ruffled fur | 1 | |
Mildly hunched back, ruffled fur | 2 | |
Severely hunched back, ruffled fur, lack of cleaning | 3 | |
Behavior and activity | Curious and alert | 0 |
Calm, mildly reduced spontaneous movement | 1 | |
Apathy, moderately reduced spontaneous movement, mildly reduced induced movement | 2 | |
Stupor, no spontaneous movement, severely reduced induced movement | 3 | |
Body weight | No change >5% | 0 |
Decrease of 5–15% | 1 | |
Decrease of 15–25% | 2 | |
Decrease of >25% | 3 |
Mouse Strain | Liver | Spleen | Brain |
---|---|---|---|
B6-IFNARtmAgt | 6/6 (7.08 × 105–6.54 × 106) | 6/6 (1.6 × 105–3.02 × 106) | 6/6 (8.03 × 102–4.76 × 103) |
C.129S7(B6)-Ifngtm1/s/J | n.d. | 3/12 (4.4 × 10−1–2.54 × 101) | n.d. |
B6-TLR3tm1Flv | n.d. | n.d. | n.d. |
B6-TLR7tm1Aki | n.d. | 5/12 (6.28 × 10−1–5.94 × 100) | n.d. |
B6-CD4tm1Mak | n.d. | n.d. | n.d. |
B6-CD8atm1Mak | n.d. | 1/6 (1 × 102) | n.d. |
Foxn1nu-/- (NUDE) | n.d. | n.d. | n.d. |
Igh-Jtm1DhuN?+N2 | 2/6 (4.08 × 10−3–8.38 × 10−2) | n.d. | n.d. |
NOD.Cg-Prkdcscid Il2rgtm1WjI/SzJ (NSG) | 6/12 (4.74 × 10−1–1.41 × 104) | 4/12 (3.53 × 10−1–3.03 × 102) | 6/12 (2.87 × 10−2–3.29 × 105) |
C57Bl/6 | n.d. | 2/9 (5.41 × 10−1–4.06 × 100) | 1/9 (2.37 × 101) |
BALB/c | n.d. | 3/12 (1.41 × 100–7.05 × 100) | n.d. |
Foxn1nu+/- (heterozygous NUDE) | n.d. | n.d. | n.d. |
NOD/ShiLtJ (NOD) | n.d. | 2/12 (1.47 × 100–5.43 × 100) | n.d. |
Mouse Strain | Histology | IHC Liver | IHC Spleen | IHC Brain | IHC Heart | IHC Lung | IHC Kidney |
---|---|---|---|---|---|---|---|
B6-IFNARtmAgt | Severe, diffuse, hepatocellular necrosis and apoptosis; Mild to moderate lymphocytolysis in the spleen | +++ | +++ | + (3/6) - (3/6) | - | + (1/6) -(5/6) | +(2/6) -(4/6) |
NOD.Cg-Prkdcscid Il2rgtm1WjI/SzJ (NSG) | Mild, multifocal, hepatocellular necrosis and apoptosis (2/12); No findings (10/12) | ++ | - | +++ | - | +(2/12) -(10/12) | ++(3/12) -(9/12) |
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Michaely, L.M.; Rissmann, M.; Keller, M.; König, R.; von Arnim, F.; Eiden, M.; Rohn, K.; Baumgärtner, W.; Groschup, M.; Ulrich, R. NSG-Mice Reveal the Importance of a Functional Innate and Adaptive Immune Response to Overcome RVFV Infection. Viruses 2022, 14, 350. https://doi.org/10.3390/v14020350
Michaely LM, Rissmann M, Keller M, König R, von Arnim F, Eiden M, Rohn K, Baumgärtner W, Groschup M, Ulrich R. NSG-Mice Reveal the Importance of a Functional Innate and Adaptive Immune Response to Overcome RVFV Infection. Viruses. 2022; 14(2):350. https://doi.org/10.3390/v14020350
Chicago/Turabian StyleMichaely, Lukas Mathias, Melanie Rissmann, Markus Keller, Rebecca König, Felicitas von Arnim, Martin Eiden, Karl Rohn, Wolfgang Baumgärtner, Martin Groschup, and Reiner Ulrich. 2022. "NSG-Mice Reveal the Importance of a Functional Innate and Adaptive Immune Response to Overcome RVFV Infection" Viruses 14, no. 2: 350. https://doi.org/10.3390/v14020350
APA StyleMichaely, L. M., Rissmann, M., Keller, M., König, R., von Arnim, F., Eiden, M., Rohn, K., Baumgärtner, W., Groschup, M., & Ulrich, R. (2022). NSG-Mice Reveal the Importance of a Functional Innate and Adaptive Immune Response to Overcome RVFV Infection. Viruses, 14(2), 350. https://doi.org/10.3390/v14020350