Superoxide-dependent and -independent pathways are involved in the transmission blocking of malaria

Superoxide plays a crucial role in innate immunity to various pathogens. We examined the role of superoxides in the transmission of malaria using gp91 (phox) knockout (X-CGD) mice that lack the ability to produce superoxide. M osquitoes that fed on X-CGD mice infected intraperitoneally with Plasmodium berghei NK65 ANKA formed more oocysts than did those that fed on control m ice at any day after infection. The number of oocysts peaked on day 5 post- infection in X-CGD and control mice and then decreased significantly after day 5 post-infection. However, on day 7 post-infection, the infectivity of gametocytes in X-CGD mice was significantly higher than that in control mic e. These results show that two pathways, superoxide-dependent and -independ ent, are involved in the host systems regulating the transmission of malari a and inhibiting gametocyte development.