Daily Plasmodium yoelii infective mosquito bites do not generate protection or suppress previous immunity against the liver stage

Abstract

BackgroundHuman populations that are naturally subjected to Plasmodium infection do not acquire complete protection against the liver stage of this parasite despite prolonged and frequent exposure. However, sterile immunity against Plasmodium liver stage can be achieved after repeated exposure to radiation attenuated sporozoites. The reasons for this different response remain largely unknown, but a suppressive effect of blood stage Plasmodium infection has been proposed as a cause for the lack of liver stage protection.MethodsUsing Plasmodium yoelii 17XNL, the response generated in mice subjected to daily infective bites from normal or irradiated mosquitoes was compared. The effect of daily-infected mosquito bites on mice that were previously immunized against P. yoelii liver stage was also studied.ResultsIt was observed that while the bites of normal infected mosquitoes do not generate strong antibody responses and protection, the bites of irradiated mosquitoes result in high levels of anti-sporozoite antibodies and protection against liver stage Plasmodium infection. Exposure to daily infected mosquito bites did not eliminate the protection acquired previously with a experimental liver stage vaccine.ConclusionsLiver stage immunity generated by irradiated versus normal P. yoelii infected mosquitoes is essentially different, probably because of the blood stage infection that follows normal mosquito bites, but not irradiated. While infective mosquito bites do not induce a protective liver stage response, they also do not interfere with previously acquired liver stage protective responses, even if they induce a complete blood stage infection. Considering that the recently generated anti-malaria vaccines induce only partial protection against infection, it is encouraging that, at least in mouse models, immunity is not negatively affected by subsequent exposure and infection with the parasite.

Influence of Host-Related Factors and Exposure to Mosquito Bites on the Dynamics of Antibody Response to Plasmodium falciparum Antigens

“…Anopheles saliva also induced IL-10 in draining lymph nodes and downregulated antigen-specific T-cell responses [ 21 ]. Repeated pre-exposure to Anopheles bites also seems to skew the response towards that of the Th1 phenotype and to protect against Plasmodium yoelii infection [ 28 ], but these results are controversial [ 29 , 30 ]. Thus, human immune responses modulated by mosquito saliva are significant and complex in altering the frequencies of several immune cell populations and of cytokine production in multiple tissues, and can last for several days in the skin and at the systemic level [ 26 ].…”

Vector saliva controlled inflammatory response of the host may represent the Achilles heel during pathogen transmission

“…As the number and the viability of sporozoites that reach the liver is an important factor for the disease development, any impact on this process can greatly alter the initial pathogen burden during systemic infection. In contrast to what was previously shown where exposure to mosquito bites did not protect against malaria infection [162,163], which could be attributed to several factors, starting from the quantity of saliva inoculated to the host [81] or the short duration of a mosquito bite [162]. It is well known that under natural conditions, some salivary components of mosquitoes induce an antibody response in humans [164][165][166][167].…”

Immunization with AgTRIO, a Protein in Anopheles Saliva, Contributes to Protection against Plasmodium Infection in Mice

“…Antisera against A. gambiae SGE diminished murine infection with Plasmodium , including the early hepatic stage of infection and parasitemia. In contrast, the natural immune response to mosquito bites does not afford protection against malaria, and experimental models of mosquito exposure do not demonstrate substantial protection against Plasmodium (Kebaier et al, 2010; Pollock et al, 2011). This may be attributed to several factors, including the quantity of saliva secreted into the host (Abdeladhim et al, 2011), the short duration of a mosquito bite (Kebaier et al, 2010), and/or the relative immunogenicity of specific proteins in the natural milieu of saliva compared with artificial hyper-immunization.…”