Inherent constraints on a polyfunctional tissue lead to a reproduction-immunity tradeoff

Abstract

Background Single tissues can have multiple functions, which can result in constraints, impaired function, and tradeoffs. The insect fat body performs remarkably diverse functions including metabolic control, reproductive provisioning, and systemic immune responses. How polyfunctional tissues simultaneously execute multiple distinct physiological functions is generally unknown. Immunity and reproduction are observed to trade off in many organisms but the mechanistic basis for this tradeoff is also typically not known. Here we investigate constraints and trade-offs in the polyfunctional insect fat body. Results Using single-nucleus sequencing, we determined that the Drosophila melanogaster fat body executes diverse basal functions with heterogenous cellular subpopulations. The size and identity of these subpopulations are remarkably stable between virgin and mated flies, as well as before and after infection. However, as an emergency function, the immune response engages the entire tissue and all cellular subpopulations produce induce expression of defense genes. We found that reproductively active females who were given bacterial infection exhibited signatures of ER stress and impaired capacity to synthesize new protein in response to infection, including decreased capacity to produce antimicrobial peptides. Transient provision of a reversible translation inhibitor to mated females prior to infection rescued general protein synthesis, specific production of antimicrobial peptides, and survival of infection. Conclusions The commonly observed tradeoff between reproduction and immunity appears to be driven, in D. melanogaster, by a failure of the fat body to be able to handle simultaneous protein translation demands of reproductive provisioning and immune defense. We suggest that inherent cellular limitations in tissues that perform multiple functions may provide a general explanation for the wide prevalence of physiological and evolutionary tradeoffs.

Correlated responses in basal immune function in response to selection for fast development in Drosophila melanogaster

“…Nutritional stress has been shown to upregulate immune function and is dependent on insulin signalling (Agrawal et al, 2016). Since fat body is the major immune as well as metabolic tissue of Drosophila (Gupta et al, 2022) it is likely that the results obtained in this study indicate immune‐metabolic trade‐offs. FEJ and FLJ populations are under selection for faster pre‐adult development with their egg to adult development time being 6.5 and 7.5 days respectively, due to which the larval duration especially the post‐critical duration is drastically reduced and thus they might be under nutritional deprivation which induces inflammation even under uninfected state.…”

“…Nutritional stress has been shown to upregulate immune function and is dependent on insulin signalling (Agrawal et al, 2016). Since fat body is the major immune as well as metabolic tissue of Drosophila (Gupta et al, 2022) Suzawa et al, 2019). We measured the transcript levels of 4eBP/ Thor as the read out of insulin signaling (Teleman et al, 2005) and found that there was significant increase in Thor level in both, FEJs and FLJs compared to JBs (Figure 6b) indicating reduced insulin signalling in them.…”

Drosophilaimmunity: theDrosocingene encodes two host defence peptides with pathogen-specific roles

“…This is probably owing to the high metabolic cost imposed by higher haemocyte numbers, reducing available fat body lipid stores [52]. Another example is the trade-off between reproduction and immunity, as both sides impose a high metabolic demand on the insect fat body in females [53][54][55]. While there is renewed attention on how positive selection promotes AMP polymorphisms, we know less about the evolutionary forces that maintains these alternate alleles [41,56,57].…”

Evolutionary adaptation to juvenile malnutrition impacts adult metabolism and impairs adult fitness inDrosophila

“…In addition, several essential amino acids (methionine, valine, isoleucine and in particular leucine, all less abundant in Selected flies) act as signaling molecules that promote protein synthesis by activating TOR complex 1 (Wolfson, et al 2016; Antikainen, et al 2017; Gu, et al 2022). Most of protein synthesis activity in adult female fat bodies is directed towards synthesizing egg proteins (Piper, et al 2017; Gupta, et al 2022). Thus, while we have not demonstrated a direct causal link, lower abundance of most essential amino acids in the Selected flies is consistent with their lower fecundity.…”