Innate immune responses against malaria in mosquito vector and human host

The aim of this project is to extract the similarities between the human host and the vector Anopheles gambiae in their innate immune responses against Plasmodium falciparum at transcriptome level.

It is known that parasites co-evolve with their hosts. The triple-genetic interaction between malaria, mosquito and man is particularly interesting to consider in this context. Several basic innate immune molecules and mechanisms are similar insects and humans. Since the parasite, P. falciparum has specifically adjusted to handling the immune system of its mosquito vector An. gambiae and its human host, we assume that some mechanisms by which the parasite circumvents the innate immune systems is used in both of its hosts. The innate immune system responds to different of pattern molecules on the intruder during an immune challenge. One example is the GPI-links of Plasmodium that are meant to give rise to a response that causes much of the disease symptoms in malaria. Other non-peptide products are certain phosphoantigens that in humans are recognized by γδTcells and causing their rapid proliferation and subsequent cytolytic activity towards P. falciparum infected red blood cells.

Interestingly, upon feeding mosquitoes with these molecules they respond by producing antioxidant proteins in addition to several known antimicrobial peptides. We are using both qRT-PCR and transcriptome sequence analyses to determine signalling pathways and molecules activated.

Current projects include:

1. Investigating effects of the phosphoantigen HMBPP fed to adult female A. gambiae by qRT-PCR and RNA sequencing.

2. RNAi knockdown of signalling pathways important for the response above followed by parasite development studies upon feeding parasite infected blood.

Our P3 security laboratory for work using the P. falciparum to infect A. gambiae mosquitoes is the only one in Sweden and one of few in Europe. Our current work is mainly suppoeted by EU 7th Framework program on Integrating Activity–Combination of Collaborative Project Coordination and Support Action (INFRAVEC), entitled Research capacity for the implementation of genetic control of mosquitoes.