The Role of Hemocytes in <b><i>Anopheles gambiae</i></b> Antiplasmodial Immunity

Abstract

Hemocytes synthesize key components of the mosquito complement-like system, but their role in the activation of antiplasmodial responses has not been established. The effect of activating Toll signaling in hemocytes on Plasmodium survival was investigated by transferring hemocytes or cell-free hemolymph from donor mosquitoes in which the suppressor cactus was silenced. These transfers greatly enhanced antiplasmodial immunity, indicating that hemocytes are active players in the activation of the complement-like system, through an effector/effectors regulated by the Toll pathway. A comparative analysis of hemocyte populations between susceptible G3 and the refractory L3-5 Anopheles gambiae mosquito strains did not reveal significant differences under basal conditions or in response to Plasmodium berghei infection. The response of susceptible mosquitoes to different Plasmodium species revealed similar kinetics following infection with P. berghei,P. yoelii or P. falciparum, but the strength of the priming response was stronger in less compatible mosquito-parasite pairs. The Toll, Imd,STAT or JNK signaling cascades were not essential for the production of the hemocyte differentiation factor (HDF) in response to P. berghei infection, but disruption of Toll, STAT or JNK abolished hemocyte differentiation in response to HDF. We conclude that hemocytes are key mediators of A. gambiae antiplasmodial responses.

Hemocyte differentiation mediates the mosquito late-phase immune response against Plasmodium in Anopheles gambiae

“…4A), STAT-A silencing renders the hemocytes nonresponsive to wild-type Plasmodium infection (Fig. 5A) in agreement with previous results that STAT-A contributes to hemocyte differentiation (26). Moreover, when SOCS (a negative regulator of the STAT pathway) is silenced, hemocytes respond normally to Plasmodium infection while displaying higher basal percentages of granulocytes (Fig.…”

“…In control dsGFP mosquitoes, significant shifts in the composition of hemocyte subpopulations were detected following ookinete invasion (MAOP vs. WT parasites) without altering total hemocyte numbers (Fig. S4A), in agreement with previous reports (21,26). Mosquitoes infected with wild-type P. berghei parasites had a reduced proportion of prohemocytes and significantly increased representation of circulating oenocytoids and granulocytes, suggesting that ookinete invasion triggers hemocyte differentiation (Fig.…”

“…Previous studies have shown that the composition of the mosquito hemocyte population is dynamic and is influenced by blood feeding and infection status (21)(22)(23)(24)(25)(26). In response to Plasmodium infection, prohemocyte precursors undergo differentiation into oenocytoid and granulocyte cell populations (21,26).…”

Blood feeding induces hemocyte proliferation and activation in the African malaria mosquito, Anopheles gambiae Giles

“…A second cellular immune response, phagocytosis of malaria parasites, has been observed after 10 days post-infection, but does not reduce significantly the parasite population (Hillyer et al, 2007). However, hemocytes contribute significantly to anti-malarial immunity (Ramirez et al, 2013), and they are the only source of many of the critical anti-parasitic humoral immune factors, including phenoloxidase (Müller et al, 1999) and TEP1 (Frolet et al, 2006).…”

“…Malaria parasite infection induces a number of significant molecular changes in hemocytes (Baton et al, 2009;Pinto et al, 2009;Rodrigues et al, 2010), which limit parasite development (Pinto et al, 2009;Ramirez et al, 2013). However, all studies to date have evaluated hemocyte responses to infection as compared with a non-infectious blood meal.…”