Abstract
Arthropod vectors have multiple physical and immunological barriers that impede the development and transmission of parasites to new vertebrate hosts. These include the peritrophic matrix (PM), a chitinious barrier that separates the blood bolus from the midgut epithelia and modulates the vector-microbiota interactions. In tsetse flies, a sleeve-like PM is continuously produced by the cardia organ located at the fore- and midgut junction. During their development in tsetse, African trypanosomes have to bypass the PM twice: first to colonize the midgut and then to reach the salivary glands (SG). However, not all flies with midgut infections develop mammalian transmissible SG infections - the reasons for which are unclear. Here, we used transcriptomics, microscopy and functional genomics analyses to dissect the factors that regulate parasite migration from midgut to SG. In flies with midgut infections only, parasites are cleared at the cardia by reactive oxygen intermediates (ROIs) at the expense of collateral cytotoxic damage to the cardia. In flies with midgut and SG infections, gene expression for components of the PM is reduced and structural integrity of the barrier is compromised. Under these circumstances trypanosomes traverse through the layers of the PM by aggregating into cyst-like bodies. The process of PM attrition that enables the parasites to reenter into the midgut lumen to move forward to SG is apparently mediated by components of the parasites residing in the cardia. Thus, a fine-tuned dialogue between tsetse and trypanosomes at the cardia determines the outcome of PM integrity and trypanosome transmission success.
Author summary Insects are responsible for transmission of parasites that cause deadly diseases in humans and animals. Understanding the key factors that enhance or interfere with parasite transmission processes can result in new control strategies. Here, we report that a proportion of tsetse flies with African trypanosome infections in their gut can prevent the parasites from migrating to the salivary glands, albeit at the expense of collateral damage. In a subset of flies with gut infections, the parasites manipulate the integrity of the gut barrier, called the peritrophic matrix, and reach the salivary glands for transmission to the next mammal. Either targeting parasite manipulative processes or enhancing peritrophic matrix integrity could reduce parasite transmission.