Successful development of Plasmodium in the mosquito is essential for the transmission of malaria. A major bottleneck in
parasite numbers occurs during midgut invasion, partly as a consequence of the complex interactions between the
endogenous microbiota and the mosquito immune response. We previously identified SRPN6 as an immune component
which restricts Plasmodium berghei development in the mosquito. Here we demonstrate that SRPN6 is differentially
activated by bacteria in Anopheles stephensi, but only when bacteria exposure occurs on the lumenal surface of the midgut
epithelium. Our data indicate that AsSRPN6 is strongly induced following exposure to Enterobacter cloacae, a common
component of the mosquito midgut microbiota. We conclude that AsSRPN6 is a vital component of the E. cloacae-mediated
immune response that restricts Plasmodium development in the mosquito An. stephensi.