Age-Specific Variation in Immune Response inDrosophila melanogasterHas a Genetic Basis

Abstract

Immunosenescence, the age-related decline in immune system function, is a general hallmark of aging. While much is known about the cellular and physiological changes that accompany immunosenescence, we know little about the genetic influences on this phenomenon. In this study we combined age-specific measurements of bacterial clearance ability following infection with whole-genome measurements of the transcriptional response to infection and wounding to identify genes that contribute to the natural variation in immunosenescence, using Drosophila melanogaster as a model system. Twenty inbred lines derived from nature were measured for their ability to clear an Escherichia coli infection at 1 and 4 weeks of age. We used microarrays to simultaneously determine genome-wide expression profiles in infected and wounded flies at each age for 12 of these lines. Lines exhibited significant genetically based variation in bacterial clearance at both ages; however, the genetic basis of this variation changed dramatically with age. Variation in gene expression was significantly correlated with bacterial clearance ability only in the older age group. At 4 weeks of age variation in the expression of 247 genes following infection was associated with genetic variation in bacterial clearance. Functional annotation analyses implicate genes involved in energy metabolism including those in the insulin signaling/TOR pathway as having significant associations with bacterial clearance in older individuals. Given the evolutionary conservation of the genes involved in energy metabolism, our results could have important implications for understanding immunosenescence in other organisms, including humans.

The development of pathogen resistance in Daphnia magna: implications for disease spread in age-structured populations

“…For example, our data highlight that there is extensive genetic variation for a late-life decline in defensive ability, which might reflect immunosenescence. Studies on other organisms have supported the theory that immunocompetence generally decreases with advanced age in invertebrates (Adamo et al, 2001;Doums et al, 2002;Kurtz, 2002;Laws et al, 2004;Prasai and Karlsson, 2012;Whitehorn et al, 2011;Zerofsky et al, 2005), but, as with the current results, there also exist examples of genetic variation for immunosenescence or where immunocompetence increases with age (Felix et al, 2012;Khan and Prasad, 2013;Lesser et al, 2006). Assuming that, in the wild, different strategies might be favoured at different times, or in different locations, this genotype × age interaction indicates a mechanism by which genetic variation may be maintained in natural populations.…”

“…What has been little studied, however, is the basic ontogeny of immunity early in the life of invertebrates. Changes in the immune system later in life (and immunosenescence in particular) have received considerable attention (Adamo et al, 2001;Doums et al, 2002;Eleftherianos et al, 2008;Felix et al, 2012;Kurtz, 2002;Laws et al, 2004;Lesser et al, 2006;Piñera et al, 2013;Prasai and Karlsson, 2012;Sorrentino et al, 2002;Whitehorn et al, 2011;Zerofsky et al, 2005), but few studies have included the first days of an invertebrate's life. The main aim of the present study was to shed light on the development of the defence system of an invertebrate, the crustacean Daphnia magna Straus, under tight experimental control.…”

Transgenerational interactions involving parental age and immune status affect female reproductive success inDrosophila melanogaster

“…Second, daughter reproductive success was highest when both daughters and their mothers had received the control immune treatment, and were thus naive to an immune activation challenge. However, daughters that received the immune challenge had higher reproductive success when produced by mothers that had also received the immune challenge, relative to mothers that had received the control, and Senescence of immune function with increasing age is well documented [23,24,26]. However, information is scarce as to the contribution of immunity-by-age interactions to phenotypic expression, and the extent to which their effects may be transmitted across generations, hence contributing to the non-genetic variance underpinning offspring phenotypic expression.…”

“…Immune capacity is known to be sensitive to age-related senescence [23][24][25][26][27], and immune-related traits are also heavily entwined in non-genetic transgenerational processes [1,3,13]. This is particularly well documented for the adaptive branch of the immune system that is present only in vertebrates [3,28].…”

Vector competence of Aedes aegypti mosquitoes for filarial nematodes is affected by age and nutrient limitation

“…Immunosenescence has been best documented in Drosophila (Eleftherianos and Castillo, 2012;Felix et al, 2012;Katewa and Kapahi, 2011;Mackenzie et al, 2011;Remolina et al, 2012), but it also seems to be common mosquitoes (Christensen et al, 1986;Chun et al, 1995;Desowitz and Chellappah, 1962;Hillyer et al, 2005;Li et al, 1992;Wang et al, 2010). Older Culex pipiens fatigans became more susceptible to the filarial nematode Brugia sp, showing a higher parasite load than younger individuals (Desowitz and Chellappah, 1962).…”