Evaluating the Costs of Mosquito Resistance to Malaria Parasites

Abstract

Costly resistance mechanisms have been cited as an explanation for the widespread occurrence of parasitic infections, yet few studies have examined these costs in detail. A malaria-mosquito model has been used to test this concept by making a comparison of the fitness of highly susceptible lines of mosquitoes with lines that are resistant to infection. Malaria infection is known to cause a decrease in fecundity and fertility of mosquitoes; resistant mosquitoes were thus predicted to be fitter than susceptible ones. Anopheles gambiae were selected for refractoriness/resistance or for increased susceptibility to infection by Plasmodium yoelii nigeriensis. Additional lines that acted as controls for inbreeding depression were raised in parallel but not exposed to selection pressure. Selections were made in triplicate so that founder effects could be detected. Resistance mechanisms that were selected included melanotic encapsulation of parasites within 24 h postinfection and the complete disappearance of parasites from the gut. Costs of immune surveillance were assessed after an uninfected feed, and costs of immune deployment were assessed after exposure to infection and to infection and additional stresses. Mosquito survivorship was unaffected by either resistance to infection or by an increased burden of infection when compared with low levels of infection. In most cases reproductive fitness was equally affected by refractoriness or by infection. Resistant mosquitoes did not gain a fitness advantage by eliminating the parasites. Costs were consistently associated with larval production and egg hatch rate but rarely attributed to changes in blood feeding and never to changes in mosquito size. No advantages appeared to be gained by the offspring of resistant mosquitoes. Furthermore, we were unable to select for refractoriness in groups of mosquitoes in which 100% or 50% of the population were exposed to infection every generation for 22 generations. Under these selection pressures, no population had become completely refractory and only one became more resistant. Variations in fitness relative to control lines in different groups were attributed to founder effects. Our conclusion from these findings is that refractoriness to malaria is as costly as tolerance of infection. KeywordsAnopheles gambiae; fitness costs; innate immunity; malaria; mosquito; Plasmodium; refractoriness Despite their detrimental effects on the host, parasitic infections are extremely common (Esch and Fernandez 1993). This observation has led evolutionary ecologists to evoke life-history theories to explain why host traits for parasite resistance are not always selected. Immune defense is deemed to be costly, and thus supposed trade-offs exist with other fitness 2 E-mail: h.hurd@keele.ac.uk 3 E-mail: p.j.taylor@keele.ac.uk 4 E-mail: bia13@keele.ac.uk 5 E-mail: bia50@keele.ac.uk 6 E-mail: p.eggleston@keele.ac.uk UKPMC Funders Group Author Manuscript UKPMC Funders Group Author Manuscript UKPMC Funders Group Author Manuscriptcomponents. Th...

Transgenic malaria-resistant mosquitoes have a fitness advantage when feeding onPlasmodium-infected blood

“…These findings offer an interesting contrast to the results of Hurd and colleagues (11,12) who reported that the parasite imposes a fitness cost on the mosquito (as we found) but that resistant mosquitoes that up-regulate natural immune responses to Plasmodium infection are not more fit than nonresistant mosquitoes, presumably because the fitness costs of being hyperimmune negate the fitness advantage of not being infected. A potential explanation for this discrepancy is that the transgenic mosquitoes used in our study are Plasmodium-refractory because of expression of a presumably harmless (2) gene (SM1) rather than activation of the endogenous innate immune cascade.…”

Genetic variation of male reproductive success in a laboratory population of Anopheles gambiae

“…The hatching success in our study was similar to other lab colonies of A. gambiae [43 – 63%; [40]], but lower than that of field-collected individuals [86%; [39]], suggesting some inbreeding effects. In mosquitoes of the genus Culex and Aedes , low hatching success is commonly caused by Wolbachia , a maternally inherited bacteria that induces cytoplasmic incompatibility where sperm from infected males are unable to fertilize the eggs of uninfected females, however, this phenomenon is not known to occur in Anopheline mosquitoes [41].…”

“…The genetic architecture of female fitness and malaria resistance has understandably been the focus of much theoretical [42,43] and empirical work [40,44] given its epidemiological significance. However, as molecular biologists reveal the abundance of genes involved in protecting female mosquitoes from malaria parasites [45-48] and as others, using a variety of insects, demonstrate the ubiquity of trade-offs between immunity and other life history traits [49-51], there is a growing awareness that unless the expression of these anti-malarial genes is perfectly sex-linked, males will play a role in their evolution.…”

Injury and immune response: applying the danger theory to mosquitoes

“…For example, how are parasites able to develop and escape from the mosquito immune response? Given that the lifespan of the mosquito is not much longer than 30 days (Grieco et al, 2003; Hurd et al, 2005), and that parasite development takes, depending on the species of Plasmodium , from 15 to 25 days, how is it possible that the mosquito can transmit the parasite to humans? Moreover, what is the nature of the signals that activate the immune response against this parasite and associated damage?…”