Malaria parasite immune evasion and adaptation to its mosquito host is influenced by the acquisition of multiple blood meals

Abstract

14A minimum of two blood meals are required for a mosquito to acquire and transmit 15 malaria, yet Anopheles mosquitoes frequently obtain additional blood meals during their 16 adult lifespan. To determine the impact of subsequent blood-feeding on parasite 17 development in Anopheles gambiae, we examined rodent and human Plasmodium 18 parasite infection with or without an additional non-infected blood meal. We find that an 19 additional blood meal significantly reduces P. berghei immature oocyst numbers, yet does 20 not influence mature oocysts that have already begun sporogony. This is in contrast to 21 experiments performed with the human parasite, P. falciparum, where an additional blood 22 meal does not affect oocyst numbers. These observations are reproduced when 23 mosquitoes were similarly challenged with an artificial protein meal, suggesting that 24 parasite losses are due to the physical distension of the mosquito midgut. We provide 25 evidence that feeding compromises the integrity of the midgut basal lamina, enabling the 26 recognition and lysis of immature P. berghei oocysts by the mosquito complement 27 system. Moreover, we demonstrate that additional feeding promotes P. falciparum oocyst 28 growth, suggesting that human malaria parasites exploit host resources provided with 29 blood-feeding to accelerate their growth. This contrasts experiments with P. berghei, 30 where the size of surviving oocysts is independent of an additional blood meal. Together, 31 these data demonstrate differences in the ability of Plasmodium species to evade immune 32 detection and adapt to utilize host resources at the oocyst stage, representing an 33 additional, yet unexplored component of vectorial capacity that has important implications 34 for transmission of malaria. 36Blood-feeding is an inherent behavior of all hematophagous arthropods, providing 37 nutritional resources for development or reproduction, while enabling the acquisition and 38 transmission of a pathogen from one host to the next. This includes a number of 39 arthropod-borne diseases that influence human health, most notably malaria, which 40 causes more than 200 million infections and 400,000 deaths every year (WHO, 2018). 41Caused by Plasmodium parasites, malaria transmission requires the bite of an Anopheles 42 mosquito, such that understanding the factors that influence vectorial capacity are integral 43 to efforts to reduce malaria transmission. 44Following the ingestion of an infectious blood-meal, malaria parasites undergo substantial 45 development in the mosquito host as they transition from gametes to a fertilized zygote, 46 a motile ookinete, an oocyst, and a sporozoite capable of transmission to a new host 47 (Smith et al., 2014). During this approximate two week period of development (referred 48 to as the extrinsic incubation period, EIP), significant bottlenecks reduce parasite 49 numbers at each of these respective Plasmodium stages (Smith et al., 2014). These 50 losses are mediated in part by the mosquito innate immune system...

Multiple blood feeding in mosquitoes shortens the Plasmodium falciparum incubation period and increases malaria transmission potential

“…Oocysts can take up labelled mosquito lipoparticles [ 36 ], and increased availability of lipids as provided by an additional blood meal may accelerate host lipid scavenging, which also occurs during human stages of infection [ 37 – 39 ]. In this study, however, depletion of Lp—the major mosquito lipid transporter—did not slow rates of oocyst growth or sporozoite appearance after a second blood feeding, with only a slight, non-significant delay in EIP 50 detected, suggesting that other nutrients (possibly amino acids, as suggested by a recent report [ 21 ]) may mediate the bulk of the observed boost in oocyst development. Lp silencing also had no effects on P .…”

“…These findings are consistent with infection studies in closely related mosquito species that showed that an additional blood meal during development either boosts P . falciparum sporozoite intensities or yields [ 22 – 26 , 34 ] or increases oocyst size [ 21 – 23 ], although none analyzed parasite growth rates after the second meal. Our study conclusively links the effects of an additional blood meal to increased parasite developmental rates and a shortened EIP.…”

“…Additional blood meals may therefore potentially influence oocyst growth and the EIP, as suggested by reports showing an additional feed can increase P . falciparum oocyst size [ 21 , 22 ] and salivary gland sporozoite numbers at a given time point [ 22 , 23 ], and can be employed to boost sporozoite yields [ 24 – 26 ].…”

20-Hydroxyecdysone Primes Innate Immune Responses That Limit Bacterial and Malarial Parasite Survival in Anopheles gambiae

“…Therefore, the effects of 20E on mosquito immunity and reproductive fitness potentially depend on specific host-pathogen interactions that define differences in An. gambiae immunity to P. berghei and P. falciparum parasites (45,61). In summary, our findings demonstrate the role of the hormone 20E in priming mosquito innate immunity to both bacteria and malaria parasites.…”

Novel insights into a well-studied steroid hormone: The impacts of 20-hydroxyecdysone (20E) on mosquito immunity

“…Therefore, the effects of 20E on mosquito immunity and reproductive fitness potentially depend on specific host-pathogen interactions that define differences in An. gambiae immunity to P. berghei and P. falciparum parasites [60,75].…”