Anopheles gambiae Blood Feeding Initiates an Anticipatory Defense Response to Plasmodium berghei

Abstract

Mosquitoes have potent innate defense mechanisms that protect them from infection by diverse pathogens. Much remains unknown about how different pathogens are sensed and specific responses triggered. Leucine-Rich repeat IMmune proteins (LRIMs) are a mosquito-specific family of putative innate receptors. Although some LRIMs have been implicated in mosquito immune responses, the function of most family members is largely unknown. We screened Anopheles gambiae LRIMs by RNAi for effects on mosquito infection by rodent malaria and found that LRIM9 is a Plasmodium berghei antagonist with phenotypes distinct from family members LRIM1 and APL1C, which are key components of the mosquito complement-like pathway. LRIM9 transcript and protein levels are significantly increased after blood feeding but are unaffected by Plasmodium or midgut microbiota. Interestingly, LRIM9 in the hemolymph is strongly upregulated by direct injection of the ecdysteroid, 20-hydroxyecdysone. Our data suggest that LRIM9 may define a novel anti-Plasmodium immune defense mechanism triggered by blood feeding and that hormonal changes may alert the mosquito to bolster its defenses in anticipation of exposure to blood-borne pathogens.

Diet-Induced Nutritional Stress and Pathogen Interference in Wolbachia-Infected Aedes aegypti

“…gallinaceum infection. It is possible that levels of H 2 O 2 , nos or the immune genes that we examined could have been changed in response to blood feeding or severity of Plasmodium infection, as both factors are linked to oxidative stress response [56, 66, 83, 84]. Additionally, there could have been systemic change in the mosquito oxidative stress and immune responses as a result of these processes, and this may have contributed to the response of Wolbachia to pathogens, even under conditions of starvation.…”

Rapid evolution of female-biased genes among four species of Anopheles malaria mosquitoes

“…Their rapidly diverging sequences and previous work showing that some of these are under strong positive selection (Arcà et al 2014) lends support to the notion that host immune pressures are a dominant driving force acting on salivary gland genes essential for blood feeding. At the same time, the presence of saglin (SG1f:AGAP000610) that acts as a binding partner for parasitic TRAP protein (Ghosh et al 2009;Upton et al 2015) but also five more members of this SG1 family may indicate the impact of pathogen-driven pressures (Fig. 5B).…”

“…5B). Among these are a cluster on Chromosome 2L containing an array of leucine-rich repeat immune proteins (LRIM 8A:AGAP007454, 8B:AGAP007456, 9:AGAP007453, and 10:AGAP007455) (Waterhouse et al 2010), of which LRIM9 knockdown increases parasite load threefold (Vlachou et al 2005;Upton et al 2015). AGAP000151 (IRSP5), whose silencing increases both bacterial and parasite numbers (Dong et al 2006), and AGAP000570 (AgSGU), which is one of the most abundant peritrophic matrix proteins (Dinglasan et al 2009) and has important roles in ookinete attachment of Plasmodium falciparum (Mathias et al 2014), were also identified.…”

Anopheles gambiae hemocytes exhibit transient states of activation

“…This obligatory blood-feeding requirement exposes female mosquitoes to a variety of microorganisms, and causes major transient changes in the mosquito gut microbiota. Not surprisingly, recent studies have led to renewed appreciation of the blood meal as a major immunostimulant for female mosquitoes (Bryant and Michel, 2014; Upton et al, 2015). Specifically, cellular immunity undergoes major shifts in the female mosquito after she blood feeds.…”