The heat shock response and humoral immune response are mutually antagonistic in honey bees

Abstract

The honey bee is of paramount importance to humans in both agricultural and ecological settings. Honey bee colonies have suffered from increased attrition in recent years, stemming from complex interacting stresses. Defining common cellular stress responses elicited by these stressors represents a key step in understanding potential synergies. The proteostasis network is a highly conserved network of cellular stress responses involved in maintaining the homeostasis of protein production and function. Here, we have characterized the Heat Shock Response (HSR), one branch of this network, and found that its core components are conserved. In addition, exposing bees to elevated temperatures normally encountered by honey bees during typical activities results in robust HSR induction with increased expression of specific heat shock proteins that was variable across tissues. Surprisingly, we found that heat shock represses multiple immune genes in the abdomen and additionally showed that wounding the cuticle of the abdomen results in decreased expression of multiple HSR genes in proximal and distal tissues. This mutually antagonistic relationship between the HSR and immune activation is unique among invertebrates studied to date and may promote understanding of potential synergistic effects of disparate stresses in this critical pollinator and social insects more broadly.

The Heat Shock Response in the Western Honey Bee (Apis mellifera) is Antiviral

“…In order to identify the heat shock proteins (HSPs) potentially involved in reducing virus levels in heat-shocked honey bees, qPCR was used to measure the expression of six candidate HSP-encoding genes 72 h post-injection in virus-infected bees relative to mock-infected (buffer-injected) bees that were either maintained at a constant temperature or exposed to heat shock post-infection ( Figure 2, Figure S1). The panel of honey bee heat shock protein encoding genes examined in these experiments included several genes that exhibited increased expression in previous transcriptome level analyses of virus-infected bees (i.e., protein lethal(2)essential for life-like, dnaj shv-like, and hsp83-like) [61], a gene involved in the unfolded protein response (i.e., hsc70-3), and core heat-shock response genes (i.e., hsc70-4, hsp83-like, and hsp90) [71]. (E) Heat shock protein 83-like (hsp83-like) expression was induced by virus infection, while heat shock reduced expression in two out of three biological replicates.…”

“…Heat shock 70-kDa protein cognate 3 (hsc70-3) is a conserved endoplasmic reticulum chaperone that functions in the unfolded protein response [71,[92][93][94]. It is induced in honey bees exposed to heat stress (i.e., 45 • C for 4 h) [71]. In Drosophila melanogaster S2 cells hsc70-3 is required for effective RNA-interference [78].…”

“…In general, heat shock proteins (HSPs) are involved in maintaining cellular protein homeostasis-protein synthesis, folding, function, and regulation of degradation (i.e., proteostasis) [70]. The heat shock response and broader proteostasis network in honey bees are conserved and the expression of core heat shock factor target genes and several members of the broader proteostasis network are induced by heat-stress [71]. There is a positive relationship between the heat shock response and immune response in other invertebrates, including Drosophila melanogaster and Caenorhabditis elegans [72][73][74][75][76].…”

“…There is a positive relationship between the heat shock response and immune response in other invertebrates, including Drosophila melanogaster and Caenorhabditis elegans [72][73][74][75][76]. However, McKinstry et al determined that heat shock factor target gene expression was reduced in response to wounding and bacterial infection in honey bees and thus concluded that the heat shock response and humoral immune responses are mutually antagonistic [71]. In the context of viral infection, HSPs can both positively and negatively affect viral replication [76][77][78][79][80][81].…”

The role of the gut microbiome in health and disease of adult honey bee workers

“…Disruption of the microbiome (dysbiosis) has many consequences for worker development: such disruption during early adult life affects expression of important developmental genes, including vitellogenin [29 • ] and is expected to affect immune system function, since the honey bee microbiome stimulates immune pathways [14 •• ,29 • ,30 • ]. In turn, honey bee innate immune function has been shown to be compromised by stimulation of cellular stress responses [31 • ]. Together these findings suggest that dysbiosis may have cascading effects for the ability of bees to respond to environmental stressors such as poor nutrition or temperature stress, and that, conversely, these stressors may impact the microbiome (Figure 2).…”