Macroimmunology: the drivers and consequences of spatial patterns in wildlife immune defense

1. Spatial variation in parasite pressure, abiotic and biotic conditions,
and anthropogenic factors can all shape immune phenotypes across spatial
scales. Identifying the most important spatial drivers of immunity could
help preempt infectious disease risks, especially in the context of how
large-scale factors such as urbanization affect defense by changing
environmental conditions. 2. We provide a synthesis of how to apply
macroecological approaches to the study of ecoimmunology (i.e.,
macroimmunology). We first review spatial factors that could generate
spatial variation in defense, highlighting the need for large-scale
studies that can differentiate competing environmental predictors of
immunity and detailing contexts where this approach might be favored over
small-scale experimental studies. We next conduct a systematic review of
the literature to assess the frequency of spatial studies and to classify
them according to taxa, immune measures, spatial replication and extent,
and statistical methods. 3. We review 210 ecoimmunology studies sampling
multiple host populations. We show that whereas spatial approaches are
relatively common, spatial replication is generally low and unlikely to
provide sufficient environmental variation or power to differentiate
competing spatial hypotheses. We also highlight statistical biases in
macroimmunology, in that few studies characterize and account for spatial
dependence statistically, potentially affecting inferences for the
relationships between environmental conditions and immune defense. 4. We
use these findings to describe tools from geostatistics and spatial
modeling that can improve inference about the associations between
environmental and immunological variation. In particular, we emphasize
exploratory tools that can guide spatial sampling and highlight the need
for greater use of mixed-effects models that account for spatial
variability while also allowing researchers to account for both
individual- and habitat-level covariates. 5. We lastly discuss future
research priorities for macroimmunology, including focusing on latitudinal
gradients, range expansions, and urbanization as being especially amenable
to spatial approaches. We highlight opportunities posed by assessing
spatial variation in host tolerance, coupling large-scale field studies
with small-scale field experiments and longitudinal approaches, and
applying statistical tools from macroecology and meta-analysis to identify
generalizable spatial patterns.