Immunological and Pharmacological Potential of the Mosquito Sialome

Mosquito bites are primarily recognized as sources of pruritus and vectors for pathogens, yet the interaction between the mosquito sialome and host immunity is profoundly more complex. Beyond facilitating pathogen transmission, mosquito saliva constitutes a pharmacologically active cocktail of anticoagulants, vasodilators, and immunomodulators that systematically alters the host's physiological response. Repeated exposure can initiate a state of immunological tolerance, marked by a decisive immunoglobulin class-switch from an IgE-mediated hypersensitivity to a non-inflammatory, IgG4-dominated response. This shift effectively attenuates the local inflammation and pruritus typically associated with bites. Furthermore, specific components of the sialome hold significant therapeutic promise. For instance, anti-inflammatory peptides from *Aedes aegypti* protect murine models from lethal endotoxin shock, while a D7 family salivary protein can directly neutralize dengue virus infectivity in both in vitro and in vivo settings. The salivary peptide sialokinin actively skews the host immune response toward a Th2 phenotype, an insight that may unlock novel vaccine strategies aimed not at the pathogen, but at the vector's saliva to disrupt transmission. This review synthesizes the compelling evidence for the immunological and biochemical benefits of the mosquito sialome, reframing these common encounters as a mechanism for immunological conditioning and a valuable source of pharmacological scaffolds for designing novel therapeutics.