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The mosquito’s innate immune system controls both Plasmodium and bacterial infections. We investigated the competitiveness of mosquitoes genetically modified to alter expression of their own anti-Plasmodium immune genes in a mixed-cage population with wild-type mosquitoes. We observed that genetically modified mosquitoes with increased immune activity in the midgut tissue did not have an observed fitness disadvantage and showed reduced microbial loads in both the midgut and reproductive organs. These changes result in a mating preference of genetically modified males for wild-type females, whereas wild-type males prefer genetically modified females. These changes foster the spread of the genetic modification in a mosquito cage population.