Abstract
Malaria parasite can encounter heterogenous hosts and different type of host cells. In particular during the intra-erythrocytic cycle the parasite replicates inside an erythrocyte and can encounter different erythrocytes in term of maturation stage or in host carrying haemoglobin variants modifying the red blood cell environment. The impact of this heterogeneity on mosquito-transmissible stages is particularly unexplored. Characterising their effects on both sexual commitment and transmission to mosquitoes is of paramount importance in the fight against malaria. Here we leveraged new technologies including single cell transcriptomics as well as samples collected in naturally infected carriers to understand the impact of RBC heterogeneity on transmission phenotypes.Firstly, we find that sickle cell trait carrier has an enhanced mosquito transmission through both an increase in prevalence of transmission stages and are more infectious to mosquitoes, suggesting they excessively contribute to malaria transmission and should be taken into account in our understanding of the spread of malaria.Secondly, we find that P. falciparum preferentially invades younger erythrocytes and that the biomass of infected reticulocyte is important within an infection. We further show that parasites preferentially commit to sex within younger erythrocytes, suggesting that the host cell is one of the key determinants in environmentally-induced sexual fate determination.Our data show cases the power of combining cutting edge methods with parasites in their natural environment as a source for identifying new and exciting parasite biology. This work has important implication for our understanding of how parasites maximise their transmission in response to a carrying environment and therefore on the spread of malaria and how it may be targeted in transmission blocking interventionsKey words: Sexual commitment, sickle cell trait, host cell preference