Effects of immune challenge on expression of life-history and immune trait expression in sexually reproducing metazoans—a meta-analysis

Background Life-history theory predicts a trade-off between investment into immune defence and other fitness-related traits. Accordingly, individuals are expected to upregulate their immune response when subjected to immune challenge. However, this is predicted to come at the expense of investment into a range of other traits that are costly to maintain, such as growth, reproduction and survival. Currently, it remains unclear whether the magnitude of such costs, and trade-offs involving immune investment and other traits, manifests consistently across species and sexes. To address this, we conducted a meta-analysis to investigate how changes in sex, ontogenetic stage and environmental factors shape phenotypic trait expression following an immune challenge. Results We explored the effects of immune challenge on three types of traits across sexually reproducing metazoans: life-history, morphological and proximate immune traits (235 effect sizes, 53 studies, 37 species [21 invertebrates vs. 16 vertebrates]). We report a general negative effect of immune challenge on survival and reproduction, a positive effect on immune trait expression, but no effect on morphology or development time. The negative effects of immune challenge on reproductive traits and survival were larger in females than males. We also report a pronounced effect of the immune treatment agent used (e.g. whether the treatment involved a live pathogen or not) on the host response to immune challenge, and find an effect of mating status on the host response in invertebrates. Conclusion These results suggest that costs associated with immune deployment following an immune challenge are context-dependent and differ consistently in their magnitude across the sexes of diverse taxonomic lineages. We synthesise and discuss the outcomes in the context of evolutionary theory on sex differences in life-history and highlight the need for future studies to carefully consider the design of experiments aimed at disentangling the costs of immune deployment.


Tables associated with Figure 3 -meta-regressions:
- Table A2.S6. This is the source data to Figure 3a for the effect of all moderators on survival (non-phylogenetic model).
- Table A2.S7. This is the source data to Figure 3b for the effect of all moderators on reproduction (nonphylogenetic model).
- Table A2.S8. This is the source data to Figure 3c for the wffect of all moderators (main effects only) on immune trait expression (nonphylogenetic model).
- Table A2.S9. This is the source data to Figure 3d for the effect of all moderators on morphology (nonphylogenetic model).

Tables associated with Figure 4 -meta-regression subsample for mating status:
- Table A2.S10. This is the source data to Figure 4a for the effect of "mating status" (virgin or mated) on survival.
- Table A2.S11. This is the source data to Figure 4b for the effect of "mating status (virgin or mated) on reproduction.
- Table A2.S12. This is the source data to Figure 4c for the effect of "mating status (virgin or mated) on immune trait expression.  Table A2.S1_1. This is the source data to Figure 2a for the effect of "life-history status" on survival (nonphylogenetic model). Since the majority of studies only assigned sex to adult individuals, sex and age were combined into one moderator consisting of three levels: adult females, adult males, and juveniles. Effect sizes used for statistical tests were lnOR. However, back-transformed values (OR) are given in brackets. Sample size of effect sizes for each group of the moderator is given in a separate column, followed by the associated number of studies in brackets.  Table A2.S1_2. This is the source data to Figure 2a for the effect of "treatment agent" (replicating agent vs. non-replicating agent) on survival (non-phylogenetic model). Effect sizes used for statistical tests were logged OR (lnOR). Sample size of effect sizes for each group of the moderator is given in a separate column, followed by the associated number of studies in brackets.  Table A2.S2_1. This is the source data to Figure 2b for the effect of "life-history status" on reproduction (non-phylogenetic model). Since the majority of studies only assigned sex to adult individuals, sex and age were combined into one moderator consisting of three levels: adult females, adult males, and juveniles. Effect sizes used for statistical tests were Hedges' g. Sample size of effect sizes for each group of the moderator is given in a separate column, followed by the associated number of studies in brackets.

ES (Hg) N ES (studies) SE CI LOWER CI UPPER
Replic. agent* -0.300 18 (7) Table A2.S2_2. This is the source data to Figure 2b for the effect of "treatment agent" (replicating agent vs. non-replicating agent) on reproduction (non-phylogenetic model). Effect sizes used for statistical tests were Hedges' g. Sample size of effect sizes for each group of the moderator is given in a separate column, followed by the associated number of studies in brackets.  Table A2.S3_1. This is the source data to Figure 2c for the effect of "life-history status" on immune trait expression (non-phylogenetic model). Since the majority of studies only assigned sex to adult individuals, sex and age were combined into one moderator consisting of three levels: adult females, adult males, and juveniles. Effect sizes used for statistical tests were Hedges' g. Sample size of effect sizes for each group of the moderator is given in a separate column, followed by the associated number of studies in brackets.  Table A2.S3_2. This is the source data to Figure 2c for the effect of "treatment agent" (replicating agent vs. non-replicating immune agent) on immune trait expression (non-phylogenetic model). Effect sizes used for statistical tests were Hedges' g. Sample size of effect sizes for each group of the moderator is given in a separate column, followed by the associated number of studies in brackets.  Table A2.S4_1. This is the source data to Figure 2d for the effect of "life-history status" on morphology (non-phylogenetic model). Since the majority of studies only assigned sex to adult individuals, sex and age were combined into one moderator consisting of three levels: adult females, adult males, and juveniles. Effect sizes used for statistical tests were Hedges' g. Sample size of effect sizes for each group of the moderator is given in a separate column, followed by the associated number of studies in brackets.

ES (Hg) N ES (studies) SE CI LOWER CI UPPER
Replic. agent -0.095 12 ( Table A2.S4_2. This is the source data to Figure 2d for the effect of "treatment agent" (replicating agent vs. non-replicating agent) on morphology (non-phylogenetic model). Effect sizes used for statistical tests were Hedges' g. Sample size of effect sizes for each group of the moderator is given in a separate column, followed by the associated number of studies in brackets.  Table A2.S5_1. This is the source data to Figure 2e for the effect of "treatment agent" (replicating agent vs. non-replicating agent) on development times (non-phylogenetic model). Effect sizes used for statistical tests were Hedges' g. Sample size of effect sizes for each group of the moderator is given in a separate column, followed by the associated number of studies in brackets. (AIC = 161.75)  Table A2.S6. This is the source data to Figure 3a for the effect of all moderators on survival (nonphylogenetic model). Effect sizes used for statistical tests were logged OR, also displaying back-transformed lnOR in brackets. Reference level for the full model is adult males that were challenged with a nonreplicating agent. AIC-values are generated from a ML model. (AIC = 120.94)

Treatment agent
Replicating agent -0.187 0.173 -0.526 0.153 Table A2.S7. This is the source data to Figure 3b for the effect of all moderators on reproduction (nonphylogenetic model). Effect sizes used for statistical tests were Hedges' g. The reference level in the full model reflects adult females that were challenged with a non-replicating agent. AIC-values are generated from a ML model.

Treatment agent
Replicating agent -0.073 0.324 -0.708 0.563 Table A2.S9. This is the source data to Figure 3d for the effect of all moderators on morphology (nonphylogenetic model). Effect sizes used for statistical tests were Hedges' g. The reference level in the full model reflects adult females that were challenged with a non-replicating agent. AIC-values are generated from a ML model.  Table A2.S10. This is the source data to Figure 4a for the effect of "mating status" (virgin or mated) on survival. Effect sizes used for statistical tests were logged OR (lnOR). Sample size of effect sizes for each group of the moderator is given in a separate column, followed by the associated number of studies in brackets. Note that all data is from invertebrates.
QM (df = 1) = 2.359, p-val = 0.125 Table A2.S11. This is the source data to Figure 4b for the efffect of "mating status" (virgin or mated) on reproduction. Effect sizes used for statistical tests were Hedges' g. Sample size of effect sizes for each group of the moderator is given in a separate column, followed by the associated number of studies in brackets. Note the there was only enough data to include invertebrate females in this analysis.
QM (df = 1) = 3.3416, p-val = 0.0675  Table A2.S12. This is the source data to Figure 4c for the effect of "mating status" (virgin or mated) on immune trait expression. Effect sizes used for statistical tests were Hedges' g. Sample size of effect sizes for each group of the moderator is given in a separate column, followed by the associated number of studies in brackets.