Journal of Mosquito Research 2024, Vol.14, No.4, 172-183 http://emtoscipublisher.com/index.php/jmr 176 Hixson et al. (2021) discovered that the dynamics of epithelial cells in the mosquito midgut are integral to the insect’s ability to manage various physiological processes and pathogen infections. Their study revealed that juvenile hormone (JH) and 20-hydroxyecdysone (20E) play crucial roles in stimulating intestinal stem cell (ISC) proliferation and differentiation during different stages of the mosquito lifecycle, such as post-emergence maturation and blood-feeding. Additionally, they found that the normal turnover of epithelial cells, influenced by the gut microbiota, contributes to the aging process and impacts mosquito longevity. In the context of infections, they highlighted how Plasmodium and arboviruses can induce cell loss, prompting epithelial repair mechanisms that enhance disease tolerance and survival of the mosquito. This underscores the significance of epithelial dynamics in the broader context of vector competence and the potential for targeted vector control strategies. 4.2 Pathogen propagation in the hemocoel Once pathogens successfully cross the midgut barrier, they enter the hemocoel, the primary body cavity of the mosquito, where they encounter the mosquito's immune system. The hemocoel provides a route for pathogens to disseminate to various tissues, including the salivary glands. However, this environment is not without challenges. The mosquito's innate immune system, including mechanisms such as phagocytosis, melanization, and lysis, actively works to limit pathogen survival and propagation (Franz et al., 2015). For example, malaria sporozoites face significant immune pressure in the hemocoel, with only a small fraction successfully invading the salivary glands. Sporozoites that fail to invade within a narrow time window are rapidly degraded (Hillyer et al., 2007). The efficiency of pathogen propagation in the hemocoel is thus a critical determinant of transmission success. 4.3 Salivary gland invasion and preparation for transmission The final step in the pathogen's journey within the mosquito is the invasion of the salivary glands, which is crucial for transmission to a new host. Pathogens must overcome the salivary gland barrier, which involves specific receptor-mediated interactions (Kumar et al., 2018). For instance, malaria parasites utilize specific carbohydrate molecules on the salivary gland surface as docking receptors for invasion. The efficiency of salivary gland invasion can be influenced by the mosquito's immune responses and the pathogen's ability to manipulate the host's physiology. Once inside the salivary glands, pathogens prepare for transmission during the mosquito's next blood meal. The salivary glands produce a complex mixture of molecules that facilitate blood feeding and can modulate the host's immune response, thereby enhancing pathogen transmission (Agarwal et al, 2017). Understanding the molecular mechanisms underlying salivary gland invasion and the factors that influence transmission efficiency is essential for developing strategies to interrupt the transmission cycle of mosquito-borne diseases (Mueller et al., 2010). 5 Transmission to Humans 5.1 Mosquito saliva and its role in pathogen transmission Mosquito saliva plays a crucial role in the transmission of pathogens to humans. During blood feeding, mosquitoes inject saliva into the host, which contains a complex mixture of bioactive components that modulate the host's immune response and facilitate pathogen transmission. For instance, mosquito saliva has been shown to contain microRNAs that can regulate gene expression and enhance the infection and establishment of pathogens such as Chikungunya virus (CHIKV). Additionally, specific salivary proteins, such as LTRIN fromAedes aegypti, have been identified to interfere with host immune signaling pathways, thereby facilitating the transmission of viruses like Zika virus (ZIKV). The presence of mosquito saliva at the bite site has been linked to increased virus transmission, host susceptibility, disease progression, and higher viremia levels. These findings underscore the importance of understanding the molecular mechanisms by which mosquito saliva influences pathogen transmission to develop effective control strategies (Figure 3) (Guerrero et al., 2020). Guerrero et al. (2020) found that mosquito saliva plays a significant role in modulating the immune response upon viral inoculation into the skin. The interaction between mosquito saliva and various immune cells, such as Langerhans cells (LCs) and dendritic cells (DCs), is crucial for the subsequent immune activation and viral replication processes. The study highlights how mosquito saliva not only delivers the virus but also influences the recruitment of neutrophils and the production of pro-inflammatory cytokines, such as IL-1β, IL-6, and TNF-α.
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