1. Genetics and Genomics
  2. Immunology and Inflammation

Effects of an IgE receptor polymorphism acting on immunity, susceptibility to infection, and reproduction in a wild rodent

  1. Klara M Wanelik  Is a corresponding author
  2. Mike Begon
  3. Janette E Bradley
  4. Ida M Friberg
  5. Joseph A Jackson
  6. Christopher H Taylor
  7. Steve Paterson
  1. Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, United Kingdom
  2. School of Life Sciences, University of Nottingham, United Kingdom
  3. School of Environment and Life Sciences, University of Salford, United Kingdom
https://doi.org/10.7554/eLife.77666
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Cite this article
  1. Klara M Wanelik
  2. Mike Begon
  3. Janette E Bradley
  4. Ida M Friberg
  5. Joseph A Jackson
  6. Christopher H Taylor
  7. Steve Paterson
(2023)
Effects of an IgE receptor polymorphism acting on immunity, susceptibility to infection, and reproduction in a wild rodent
eLife 12:e77666.
https://doi.org/10.7554/eLife.77666
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1 figure, 18 tables and 1 additional file

Figures

Figure 1
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Effects of GC haplotype (hGC).

Upper panel: males. Lower panel: females: (A) Unstimulated immune gene expression: Barcode plots showing enrichment of the GO terms GO:0050729 (pro-inflammatory genes) and GO:0050728 (anti-inflammatory genes) in unstimulated splenocytes taken from individuals with (hGC+) vs. without (hGC-) the haplotype, showing that males with the haplotype have a pro-inflammatory bias, whereas females have an anti-inflammatory bias. In each plot, x-axis shows log fold change (logFC) in hGC+ vs. hGC-, black bars represent genes annotated with the GO terms and the worm shows relative enrichment. (B) Susceptibility to infection: association between hGC and the odds of infection with Babesia microti, showing that females with the haplotype have an increased susceptibility to infection (from a GLMM). (C) Reproduction: association between hGC and reproductive success, showing that males with the haplotype have lower reproductive success (from a GLM) (error bars represent ± standard error; *p<0.05; **p<0.01; see Table 1 for sample sizes). GLM = generalized linear model; GLMM = generalized linear mixed effects model.

Tables

Table 1
Model specifications including, for each main model, covariates included in the full model, datasets used, and sample sizes (F = included as a fixed effect; R = included as a random effect).
DGE analysisHaplotype association analyses
Response variable
Immune gene expressionParasite infectionReproductive successSOD1activity
Covariates
Snout-vent length		FF
Eye lens weightFF
Reproductive statusFFF
Body conditionFFF
Birth monthF
Culled or notF
SiteF; R (Il17a LMM)F (Macro); R (Micro)FF
YearFFFF
SeasonF; R (Il17a LMM)F (Macro); R (Micro)F
Individual IDR (Micro)
Assay plateR (Il17a LMM)
DatasetCCC (Macro)
L (Micro)		C+LC
Sample size♀31 ♂53Il17a LMM: ♀73 ♂220Macro: ♀82 ♂235
B. microti: ♀1075 ♂1247
Bartonella spp.: ♀1283 ♂1104		♀419
♂232		♀81
♂227

  1. C = cross-sectional; L = longitudinal; DGE = differential gene expression; LMM = linear mixed effects model.

Appendix 1—table 1
Position of single-nucleotide polymorphisms (SNPs) and other key features in the Fcer1a gene.

Features lie in scaffold CADCXT010006977 within assembly GCA_902806775.

FeatureStartEnd
Fcer1a gene1074552810745528
Exon 51074552810745881
Exon 41074681810747076
Exon 31074860910748864
Exon 21075004410750065
Exon 11075046510750642
5’ UTR1075052010750642
CDS1075046510750520
CDS1075004410750065
CDS1074860910748864
CDS1074681810747076
CDS1074572910745881
3’ UTR1074552810745729
SNP 21074871810748719
SNP 11074684610746847
Appendix 1—table 2
Top 10 annotated genes that were differentially expressed between males with vs. without the GC haplotype, including associated log fold changes (logFC), p-values, and q-values (false discovery rate [FDR]-corrected p-values).
GeneProteinLogFCp-valueq-value
Snai3Snail family zinc finger 31.6981.220 × 10–91.574 × 10–5
Pla2g4cPhospholipase A2, group IVC (cytosolic, calcium-independent)2.9046.386 × 10–94.120 × 10–5
Il33Interleukin 332.7561.474 × 10–74.755 × 10–4
Mmp13Matrix metallopeptidase 132.5714.427 × 10–71.142 × 10–3
Uba7Ubiquitin-like modifier activating enzyme 70.7715.979 × 10–71.286 × 10–3
Robo4Roundabout guidance receptor 40.8923.738 × 10–64.385 × 10–3
TtnTitin1.6658.995 × 10–67.254 × 10–3
FlncFilamin C, gamma1.5541.245 × 10–59.447 × 10–3
Crb2Crumbs family member 21.3271.567 × 10–51.063 × 10–2
Muc16Mucin 161.9371.971 × 10–51.156 × 10–2
Appendix 1—table 3
Annotated genes that were differentially expressed (q ≤ 0.1) between females with vs. without the GC haplotype, including associated log fold changes (logFC), p-values, and q-values (false discovery rate [FDR]-corrected p-values).
GeneProteinLogFCp-valueq-value
Tldc1TBC/LysM associated domain containing 11.4892.502 × 10–83.228 × 10–4
Peg3Paternally expressed 31.4405.369 × 10–50.049
Socs3Suppressor of cytokine signaling 31.0716.061 × 10–50.052
Appendix 1—table 4
Top 10 annotated genes that were differentially expressed between males with vs. without the GC haplotype when controlling for cestode burden, including associated log fold changes (logFC), p-values, and q-values (false discovery rate [FDR]-corrected p-values).
GeneProteinLogFCp-valueq-value
Il33Interleukin 333.0912.473 × 10–103.191 × 10–6
Snai3Snail family zinc finger 31.6725.259 × 10–93.393 × 10–5
Pla2g4cPhospholipase A2, group IVC (cytosolic, calcium-independent)2.8831.562 × 10–86.721 × 10–5
Uba7Ubiquitin-like modifier activating enzyme 70.8092.477 × 10–87.990 × 10–5
Mmp13Matrix metallopeptidase 132.6064.090 × 10–78.796 × 10–4
Robo4Roundabout guidance receptor 40.8928.160 × 10–69.572 × 10–3
TtnTitin1.5992.532 × 10–51.951 × 10–2
FlncFilamin C, gamma1.4932.721 × 10–51.951 × 10–2
Crb2Crumbs family member 21.2613.512 × 10–52.151 × 10–2
Appendix 1—table 5
Annotated genes that were differentially expressed (q ≤ 0.1) between females with vs. without the GC haplotype when controlling for cestode burden, including associated log fold changes (logFC), p-values, and q-values (false discovery rate [FDR]-corrected p-values).
GeneProteinLogFCp-valueq-value
Tldc1TBC/LysM associated domain containing 11.4892.890 × 10–83.730 × 10–4
Socs3Suppressor of cytokine signaling 31.0834.133 × 10–50.041
Peg3Paternally expressed 31.4116.375 × 10–50.055
Ppp1r3cProtein phosphatase 1, regulatory (inhibitor) subunit 3C1.6628.798 × 10–50.071
Appendix 1—table 6
Significance values from hapassoc models for expression of 18 genes (assayed by Q-PCR) in splenocytes.

Splenocytes were stimulated with anti-CD3 and anti-CD28 antibodies in order to promote the proliferation of T-cells. q-values (false discovery rate [FDR]-corrected p-values) are reported alongside original p-values for the genotype by sex interaction.

Genep-valueq-value
Cd40.1240.822
Cd8a0.7440.866
Foxp30.4990.845
Gata30.5630.845
Il100.8660.866
Mpo0.1730.822
Tbx210.6500.866
Tgfb10.2710.822
Ifng0.3990.822
Il17a0.0020.037
Il1b0.7490.866
Il60.2820.822
Ms4a10.2810.822
Orai10.3530.822
Tnfa0.8580.866
Il20.4110.822
Apobr0.8570.866
Arg10.5520.845
Appendix 1—table 7
Estimates, standard errors, and z-statistics from best LMM for Yeo-Johnson-transformed Il17a expression levels.
EstimateSEz
(Intercept)0.1070.0234.61
Genotype–0.1150.037–3.10
Sex male–0.0550.019–2.89
Year 20160.0840.0184.60
Genotype × sex male0.1430.0443.25
Appendix 1—table 8
Effect sizes, standard errors, z-statistics, and associated significance from Gaussian hapassoc model for SOD1 activity.
EstimateSEzp-value
(Intercept)0.6141.5140.4060.685
hAT–0.4530.223–2.0320.042
Reproductive status active–0.1120.266–0.4220.673
Sex male0.0310.2500.1240.901
SVL0.0160.0170.9450.345
Lens weight 20.5680.5311.0700.284
Lens weight 30.4400.5490.8010.423
Lens weight 40.4450.5870.7580.448
Lens weight 50.4150.6530.6360.525
Lens weight 60.3010.7520.4000.689
Lens weight 7–0.3071.095–0.2800.779
Body condition0.0200.0300.6770.498
Site CHE1.4290.4313.3160.001
Site COL2.6751.0992.4340.015
Site GRD1.4760.4373.3790.001
Site RAV0.9040.9180.9840.325
Site SCP1.1070.4192.6430.008
Year 20160.5930.2422.4570.014
Season early summer–0.3920.389–1.0070.314
Season late summer–0.0980.266–0.3690.712
Season spring–0.9690.383–2.5290.011
Appendix 1—table 9
Effect sizes, standard errors, and z-statistics from best binomial GLMM for probability of infection with Babesia microti.
EstimateSEz
(Intercept)–2.2140.377–5.87
Genotype1.2540.4163.02
Sex male0.9570.2294.19
Year 20161.2600.2774.55
Year 20171.0470.3023.46
Reproductive status active0.7540.1445.24
Body condition0.0440.0162.76
Genotype × sex male–1.1160.615–1.82
Appendix 1—table 10
Effect sizes, standard errors, and z-statistics from best binomial GLMM for probability of infection with Bartonella spp.
EstimateSEz
(Intercept)0.2360.3690.64
Year 20160.7400.1355.49
Year 20172.2800.17513.01
Appendix 1—table 11
Effect sizes, standard errors, z-statistics, and associated significance from Gaussian hapassoc model for macroparasite infection summarized by a single principal component.
EstimateSEzp-value
(Intercept)0.0500.3310.1520.879
hAC–0.1020.130–0.7860.432
hAT–0.1080.158–0.6820.495
Sex male–0.2710.126–2.1460.032
Season early summer–0.1030.182–0.5670.571
Season late summer0.0120.1320.0900.929
Season spring0.3270.1761.8540.064
Reproductive status active–0.2220.119–1.8680.062
Body condition–0.0190.014–1.3280.184
Year 2016–0.4730.124–3.8100.000
Site CHE0.7140.2263.1570.002
Site COL0.7620.5751.3270.185
Site GRD0.7070.2293.0900.002
Site RAV1.1000.4812.2880.022
Site SCP0.7470.2203.3890.001
Appendix 1—table 12
Effect sizes, standard errors, z-statistics, and associated significance from best quasi-Poisson GLM for reproductive success in males.
EstimateSEzp-value
(Intercept)1.7430.2437.1711.05 × 10–11
Genotype–0.4840.237–2.0420.042
Year 20160.5920.1853.1930.002
Year 2017–0.4370.199–2.1930.029
Birth month–0.3580.048–7.4491.97 × 10–12
Culled yes0.4220.1502.8090.005
Appendix 1—table 13
Effect sizes, standard errors, z-statistics, and associated significance from best quasi-Poisson GLM for reproductive success in females.
EstimateSEzp-value
(Intercept)1.1370.2644.2982.15 × 10–5
Year 20160.5200.2112.4660.014
Year 2017–0.1180.215–0.5490.584
Birth month–0.2980.047–6.3914.42 × 10–10
Appendix 1—table 14
Effect sizes, standard errors, z-statistics, and associated significance from best quasi-Poisson GLM for reproductive success in males when controlling for Babesia microti and Bartonella spp. infection.
EstimateSEzp-value
(Intercept)1.4670.4183.5137.64 × 10–4
Genotype–1.0810.425–2.5440.013
Year 20160.2380.2790.8540.396
Year 2017–0.9120.386–2.3380.022
Birth month–0.4640.091–5.0902.69 × 10–6
Proportion of samples Babesia-positive0.8490.2763.0760.003
Proportion of samples Bartonella-positive0.9970.4402.2680.026
Appendix 1—table 15
Effect sizes, standard errors, z-statistics, and associated significance from best quasi-Poisson GLM for reproductive success in females when controlling for Babesia microti and Bartonella spp. infection.
EstimateSEzp-value
(Intercept)1.4830.3054.8673.20 × 10–6
Birth month–0.3100.073–4.2294.38 × 10–5
Proportion of samples Babesia-positive0.5690.2472.3080.0226
Appendix 1—table 16
Panel of 18 genes for which expression levels in splenocytes stimulated with anti-CD3 and anti-CD28 antibodies were measured using two-step reverse transcription quantitative PCR (Q-PCR).
GeneProtein
Cd4T-cell surface glycoprotein CD4
Cd8aT-cell surface glycoprotein CD8 alpha chain
Foxp3Forkhead box protein P3
Gata3GATA binding protein 3
Il10Interleukin-10
MpoMyeloperoxidase
Tbx21T-box transcription factor TBX21
Tgfb1Transforming growth factor beta 1
IfngInterferon gamma
Il17aInterleukin-17a
Il1bInterleukin-1 beta
Il6Interleukin-6
Ms4a1B-lymphocyte antigen CD20
Orai1Calcium release-activated calcium channel protein 1
TnfaTumor necrosis factor alpha
Il2Interleukin-2
ApobrApolipoprotein B receptor
Arg1Arginase-1
Appendix 1—table 17
Loadings from principal component analysis summarizing infection by macroparasites (ticks, fleas, and cestodes).
MacroparasitePC1
Cestodes–0.481
Ticks–0.592
Fleas–0.646

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  1. Klara M Wanelik
  2. Mike Begon
  3. Janette E Bradley
  4. Ida M Friberg
  5. Joseph A Jackson
  6. Christopher H Taylor
  7. Steve Paterson
(2023)
Effects of an IgE receptor polymorphism acting on immunity, susceptibility to infection, and reproduction in a wild rodent
eLife 12:e77666.
https://doi.org/10.7554/eLife.77666