How microbe density affects host fitness (an ecological measure of disease tolerance) is an important problem in infection biology and microbial pathogenesis (Råberg et al., 2009, Graham et al., 2011). This question has been relatively well-studied in several organisms, from mammals to model insects (Råberg et al., 2007, Louie et al., 2016, Torres et al., 2016, Gupta and Vale, 2017, Prakash et al., 2022). In mosquitoes, higher disease tolerance enhanced vector capacity and transmission of dog heartworm in a natural population of Aedes albopictus (Dharmarajan et al., 2019), but the molecular mechanisms of how disease tolerance operates in mosquitoes are only beginning to be explored (Goic et al. 2016). In theory, the manipulation of insect physiology to inhibit disease tolerance could increase vector mortality, providing a biotechnological strategy for arbovirus control (Lambrechts and Saleh, 2019, Oliveira et al., 2020).

Here, we applied dose-response curves to study Aedes aegypti survival upon exposure to different microbes (bacteria and arbovirus) to understand the distribution of mosquito susceptibility (Pessoa et al., 2014, Ben-Ami et al., 2010). We infected Aedes aegypti through injection (systemic infection) or feeding (midgut infection) with varying doses of the model intracellular pathogen Listeria monocytogenes or the epidemiologically relevant flaviviruses Dengue and Zika. Listeria monocytogenes is an intracellular bacterium able to adapt and grow in various conditions (Toledo-Arana et al. 2009). It is frequently used as a model pathogen (Cossart, 2011) due to its ability to cross anatomical barriers, well-described mechanisms of virulence, and interactions with vertebrate and invertebrate host cells, including insects (Mansfield et al., 2003, Shirasu-Hiza and Schneider, 2007). Dengue and Zika are flaviviruses transmitted by mosquitoes and responsible for significant human morbidity and mortality worldwide (Cattarino et al. 2020). How varying initial microbe loads modulate Aedes aegypti survival remains to be systematically studied. This question was explored in the following experiments.