The immunoglobulin superfamily and the toll and IMD pathways: Essential immune responses of Anopheles gambiae against Plasmodium falciparum and other pathogens.

摘要

Mosquito immune responses are interesting primarily because they serve as vectors of human disease such as malaria. A deeper understanding of how Anopheles gambiae uses its immune responses to combat malaria parasites are likely to lead to novel methods for vector-based malaria control efforts. To this end, we have probed both immune effector genes and immune signaling pathways in an effort to identify an immune mechanism that could be exploited for malaria control. Using sequence analysis, high density DNA microarrays and RNA-interference to silencing specific genes, we showed for the first time that mosquito proteins containing immunoglobulin domains were essential regulators of immune responses to multiple pathogens including Gram positive and Gram negative bacteria and both the human and rodent malaria parasites. These same techniques coupled with real time quantitative PCR, and traditional analyses of mosquito fitness, we also showed for the first time that mosquitoes can be treated with dsRNA to give them an "immune boost" prior to parasite infection which causes them to resist that infection while not suffering a noticeable loss in fitness. These mosquitoes are refractory to infection with the human malaria parasite, P. falciparum. We have elucidated at least some of the effector molecules and signaling pathways mediating this response, primarily the IMD immune pathway. Knowing this, we endeavored to learn about the physiological nuances that allow such resistance to occur and the consequences this immune boosting may have on the mosquito's endogenous gut bacteria and fitness.