Warmer sicker? Or warmer stronger? How climate change shapes mosquito immunity.

Over the past century, global temperatures have risen by 1.1°C. Each summer, we experience record-breaking heat, but climate change extends beyond rising temperatures, it is also the cause for more frequent and intense extreme weather events. These changes are reshaping natural environments, affecting biodiversity, and influencing the distribution of many species including mosquitoes, which are vectors of harmful viruses. This has significant implications for the spread of mosquito-borne diseases like dengue, Zika, and chikungunya, putting nearly 3.9 billion people at risk worldwide.
One species of particular concern is the Asian tiger mosquito, Aedes albopictus. Originally from Southeast Asia, Ae. albopictus has colonised temperate regions of the world, like Europe and North America, over the past 60 years. Because mosquitoes are ectothermic, rising temperatures affect their behaviour, life cycle, physiology and immunity. However, key phenotypical and physiological traits that help mosquitoes to cope with high temperatures remain largely unexplored. To investigate this, I (Ayda) have been studying how Ae. albopictus mosquitoes respond to both single- or multi-generational exposure to warm temperatures, simulating different climate change scenarios. To mimic climate change as a gradual increase in average temperature, I reared over 60,000 mosquitoes for two years under a warm thermal regime (32 °C) modelled after a summer day in August in Rome. These mosquitoes evolved under these conditions for ten generations, which are roughly equivalent to three years in nature. To simulate a heat wave, characterized by short-term temperature fluctuations that can last days or months, I reared mosquitoes under the same warm thermal conditions, but only for a single generation. I then compared the life history traits of warm-acclimated (one generation) and warm-evolved (ten generations) mosquitoes to those reared under standard laboratory conditions.
When infected with any virus, mosquitoes have two ways of protecting themselves: fighting the virus, to clear the infection, or maintaining health despite a constant presence of the virus. The first strategy is widely known in vector biology and immunology and is called resistance. The second one, known as tolerance, is a less known response to infections that is gaining interest in both fields. Organisms that act as vectors of viral diseases (such as Aedes mosquitoes) have high tolerance by definition. To transmit a virus from one human to another, mosquitoes must feed on an infected person, acquire the virus, develop an infection, let the virus reach their salivary glands and then bite another person. The length of this process can be highly variable but to be an effective vector all mosquitoes need to remain healthy through the whole process while being infected with a high viral load. Despite the importance that tolerance has in the transmission of viral diseases, still little is known about how Aedes mosquitoes tolerate viral infections: trying to shed some light on these processes has been my (Hugo) main project for the past two years.
When thinking about how temperature will affect mosquito-virus interactions there are still questions that remain unanswered. Previous studies exposing mosquitoes at elevated temperatures during either their immature or adult stages have shown higher prevalence of infection, dissemination and transmission rates of arboviruses in Ae. albopictus and Ae. aegypti. However, simply rearing a part of mosquito life cycle at the suboptimal temperatures does not fully capture the broader, long-term effects of global warming. Therefore, one simple but crucial question to ask is: how does single- and multi-generational exposure to higher temperatures affect a mosquito immune response to viral challenges? This raises further questions: does heat exposure activate the mosquito immune system therefore allowing them to tolerate higher concentrations of the virus? Or does it have the opposite effect, making them more vulnerable to infection?

To tackle these questions, we (Hugo and Ayda) worked at the intersection of thermal biology and vector immunology. We investigated how tolerance and resistance to the cell-fusing agent virus (CFAV), the best characterized insect specific virus (ISV) found in mosquitoes, shift in Ae. albopictus that have been either warm-acclimated or warm-evolved.
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