Natural variation in the contribution of microbial density to inducible immune dynamics

Immune responses evolve to balance the benefits of microbial killing
against the costs of autoimmunity and energetic resource use. Models that
explore the evolution of optimal immune responses generally include a term
for constitutive immunity, or the level of immunological investment prior
to microbial exposure, and for inducible immunity, or investment in immune
function after microbial challenge. However, studies rarely consider the
functional form of inducible immune responses with respect to microbial
density, despite the theoretical dependence of immune system evolution on
microbe- versus immune-mediated damage to the host. In this study, we
analyze antimicrobial peptide (AMP) gene expression from seven wild-caught
flour beetle populations (Tribolium spp.) during acute infection with the
virulent bacteria Bacillus thuringiensis (Bt) and Photorhabdus luminescens
(P.lum) to demonstrate that inducible immune responses mediated by the
humoral IMD pathway exhibit natural variation in both microbe
density-dependent and independent temporal dynamics. Beetle populations
that exhibited greater AMP expression sensitivity to Bt density were also
more likely to die from infection, while populations that exhibited higher
microbe density-independent AMP expression were more likely to survive P.
luminescens infection. Reduction in pathway signaling efficiency through
RNAi-mediated knockdown of the imd gene reduced the magnitude of both
microbe-independent and dependent responses and reduced host resistance to
Bt growth, but had no net effect on host survival. This study provides a
framework for understanding natural variation in the flexibility of
investment in inducible immune responses and should inform theory on the
contribution of non-equilibrium host-microbe dynamics to immune system
evolution.