Clin Exp Otorhinolaryngol.  2020 Nov;13(4):396-406. 10.21053/ceo.2019.01837.

Strain-Specific Differences in House Dust Mite (Dermatophagoides farinae)-Induced Mouse Models of Allergic Rhinitis

• Lee KI
• Bae JS
• Kim EH
• Kim JH
• Lyu L
• Chung YJ
• Mo JH

• KMID: 2508516
• DOI: http://doi.org/10.21053/ceo.2019.01837

Abstract

Objectives
. Limited information is available regarding strain-related differences in mouse models of allergic rhinitis induced by Dermatophagoides farinae (Der f1). In this study, we compared differences between two mouse strains and determined the optimal dose of Der f1 for allergic rhinitis mouse models.
Methods
. Forty-eight mice were assigned to the following six groups (n=8 per group): group A (control, BALB/c), group B (Der f1-sensitized BALB/c, 25 µg), group C (Der f1-sensitized BALB/c, 100 µg), group D (control, C57BL/6), group E (Der f1-sensitized C57BL/6, 25 µg), and group F (Der f1-sensitized C57BL/6, 100 µg). Allergic inflammation was induced with Der f1 and alum sensitization, followed by an intranasal challenge with Der f1. Rubbing and sneezing scores, eosinophil and neutrophil infiltration, and immunoglobulin, cytokine, and chemokine levels in the nasal mucosa and from splenocyte cultures were assessed.
Results
. Rubbing and sneezing scores were higher in groups B, C, E, and F than in groups A and D, with a similar pattern in both strains (i.e., group B vs. E and group C vs. F). Serum immunoglobulin levels were significantly elevated compared to the control in groups B and C, but not in groups E and F. Eosinophil and neutrophil infiltration increased (all P<0.05) after the Der f1 challenge (groups B, C, E, and F) compared to the control (groups A and D) in both the BALB/c and C57BL/6 strains, without any significant difference between the two strains (group A vs. D, group B vs. E, and group C vs. F) (P>0.05). BALB/c mice (group B) showed a greater elevation of splenic interleukin (IL)-4 (P<0.01), IL-5 (P<0.01), and IL-6 levels (P<0.05) and nasal IL-4 mRNA levels (P<0.001) than the C57BL/6 mice (group E). Interestingly, mice treated with 100 µg Der f1 showed a weaker allergic response than those treated with 25 µg.
Conclusion
. We found 25 µg to be a more appropriate dose for Der f1 sensitization. BALB/c mice are more biased toward a Th2 response and are a more suitable model for allergic rhinitis than C57BL/6 mice. This study provides information on the appropriate choice of a mouse model for allergic rhinitis.

Keyword

Animal Model; Allergic Rhinitis; Mice; Dermatophagoides Farinae; Immunoglobulin

Figure

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  Fig. 1. Experimental protocol. Group A, control group of BALB/c mice; Group B, BALB/c mice exposed to 25 µg of Dermatophagoides farinae (Der f1); Group C, BALB/c mice exposed to 100 µg of Der f1; Group D, control group of C57BL/6 mice; Group E, C57BL/6 mice exposed to 25 µg of Der f1; Group F, C57BL/6 mice exposed to 100 µg of Der f1; PBS, phosphate buffered saline.

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  Fig. 2. Rubbing and sneezing counts. Control group of BALB/c mice (group A), BALB/c mice exposed to 25 µg of Dermatophagoides farinae (Der f1; group B), BALB/c mice exposed to 100 µg of Der f1 (group C), control group of C57BL/6 mice (group D), C57BL/6 mice exposed to 25 µg of Der f1 (group E), and C57BL/6 mice exposed to 100 µg of Der f1 (group F). Bars represent standard error. Significantly different from control mice, *P<0.05.

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  Fig. 3. Serum immunoglobulin (Ig) levels. (A) Total IgE levels from serum. (B) Der f1-specific IgE levels from serum. (C) Der f1-specific IgG1 levels from serum. (D) Der f1-specific IgG2a levels from serum. Control group of BALB/c mice (group A), BALB/c mice exposed to 25 µg of Dermatophagoides farinae (Der f1; group B), BALB/c mice group exposed to 100 µg of Der f1 (group C), control group of C57BL/6 mice (group D), C57BL/6 mice exposed to 25 µg of Der f1 (group E), and C57BL/6 mice exposed to 100 µg of Der f1 (group F). Bars represent standard error. Significantly different from control mice or significantly different between strains, *P<0.05, **P<0.01, ***P<0.001.

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  Fig. 4. Eosinophil infiltration in the nasal mucosa. (A) Representative microphotographs (×400), and (B) quantitative analyses of eosinophil infiltration in the nasal mucosa. The panels show Sirius Red staining (×400). Control group of BALB/c mice (group A), BALB/c mice exposed to 25 µg of Dermatophagoides farinae (Der f1; group B), BALB/c mice group exposed to 100 µg of Der f1 (group C), control group of C57BL/6 mice (group D), C57BL/6 mice exposed to 25 µg of Der f1 (group E), and C57BL/6 mice exposed to 100 µg of Der f1 (group F). PBS, phosphate buffered saline; HPF, high-power field. Bars represent standard error. Significantly different from control mice, *P<0.05, **P<0.01, ***P<0.001.

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  Fig. 5. Infiltration of neutrophils in the nasal mucosa. The panels show immunohistochemical findings for neutrophils (×400). Control group of BALB/c mice (group A), BALB/c mice exposed to 25 µg of Dermatophagoides farinae (Der f1; group B), BALB/c mice group exposed to 100 µg of Der f1 (group C), control group of C57BL/6 mice (group D), C57BL/6 mice exposed to 25 µg of Der f1 (group E), and C57BL/6 mice exposed to 100 µg of Der f1 (group F). PBS, phosphate buffered saline; HPF, high-power field. Bars represent standard error. Significantly different from control mice, *P<0.05, **P<0.01.

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  Fig. 6. Expression of interleukin (IL)-25 in the nasal mucosa. The panels show immunohistochemical findings for IL-25 (×400). Control group of BALB/c mice (group A), BALB/c mice exposed to 25 µg of Dermatophagoides farinae (Der f1; group B), BALB/c mice group exposed to 100 µg of Der f1 (group C), control group of C57BL/6 mice (group D), C57BL/6 mice exposed to 25 µg of Der f1 (group E), and C57BL/6 mice exposed to 100 µg of Der f1 (group F). PBS, phosphate buffered saline; HPF, high-power field. Bars represent standard error. Significantly different from control mice or significantly different between strains, *P< 0.05, **P< 0.01.

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  Fig. 7. Expression of interleukin (IL)-33 in the nasal mucosa. The panels show immunohistochemical findings for IL-33 (×400). Control group of BALB/c mice (group A), BALB/c mice exposed to 25 µg of Dermatophagoides farinae (Der f1; group B), BALB/c mice group exposed to 100 µg of Der f1 (group C), control group of C57BL/6 mice (group D), C57BL/6 mice exposed to 25 µg of Der f1 (group E), and C57BL/6 mice exposed to 100 µg of Der f1 (group F). PBS, phosphate buffered saline; HPF, high-power field.

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  Fig. 8. Nasal mRNA expression of cytokines. Shown are interleukin (IL)-4 (A), IL-5 (B), IL-6 (C), IL-10 (D), IL-17 (E), and interferon (IFN)-γ (F) levels in the control group of BALB/c mice (group A), BALB/c mice exposed to 25 µg of Dermatophagoides farinae (Der f1; group B), BALB/c mice group exposed to 100 µg of Der f1 (group C), control group of C57BL/6 mice (group D), C57BL/6 mice exposed to 25 µg of Der f1 (group E), and C57BL/6 mice exposed to 100 µg of Der f1 (group F). Bars represent standard error. Significantly different from control mice or significantly different between strains, ***P<0.001.

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  Fig. 9. Nasal mRNA expression of chemokines. Shown are eotaxin-1 (A), eotaxin-2 (B), CXCL1 (C), and CXCL2 (D) in the control group of BALB/c mice (group A), BALB/c mice exposed to 25 µg of Dermatophagoides farinae (Der f1; group B), BALB/c mice group exposed to 100 µg of Der f1 (group C), control group of C57BL/6 mice (group D), C57BL/6 mice exposed to 25 µg of Der f1 (group E), and C57BL/6 mice exposed to 100 µg of Der f1 (group F). Bars represent standard error. Significantly different from control mice or significantly different between strains, *P<0.05, **P<0.01, ***P<0.001.

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  Fig. 10. Cytokine levels from splenocyte culture; interleukin (IL)-4 (A), IL-5 (B), IL-6 (C), IL-10 (D), IL-17 (E) and interferon (IFN)-γ (F) in the control group of BALB/c mice (group A), BALB/c mice exposed to 25 µg of Dermatophagoides farinae (Der f1; group B), BALB/c mice group exposed to 100 µg of Der f1 (group C), control group of C57BL/6 mice (group D), C57BL/6 mice exposed to 25 µg of Der f1 (group E), and C57BL/6 mice exposed to 100 µg of Der f1 (group F). Bars represent standard error. Significantly different from control mice or significantly different between strains, *P<0.05, **P<0.01, ***P<0.001.

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