Adaptations to haematophagy: Investigations on how male and female Culex quinquefasciatus (Diptera: Culicidae) deal with human complement activation after a blood meal.

Culex quinquefasciatus is a mosquito species with an anthropophilic habit, often associated with areas with poor sanitation in tropical and urban regions. Adult males and females feed on sugars but only females feed on blood in natural conditions for egg maturation. During haematophagy, female C. quinquefasciatus transmit pathogens such as the West Nile virus, Oropouche virus, various encephalitis viruses, and Wuchereria bancrofti to human hosts. It has been observed in laboratory conditions that male C. quinquefasciatus may feed on blood during an artificial feed. Experiments were carried out to understand how males and females of this species deal with human complement activation. Our results showed that female C. quinquefasciatus, but not males, withstand the stress caused by the ingestion of normal human serum. It was observed that the salivary gland extracts from female mosquitoes were able to inhibit the classical and lectin pathways, whereas male salivary gland extracts only inhibited the lectin pathway. The male and female intestinal contents inhibited the classical and lectin pathways. Neither the salivary glands nor the intestinal contents from males and females showed inhibitory activity towards the alternative pathway. However, the guts of male and female C. quinquefasciatus captured factor H from the human serum, permitting C3b inactivation to its inactive form iC3b, and preventing the formation of the C3 convertase. The activity of the antioxidant enzyme catalase is similar in C. quinquefasciatus females and males. This article shows for the first time that males from a haematophagous arthropod species present human anti-complement activity in their salivary gland extracts and gut contents. The finding of an activity that helps to protect the damage caused by blood ingestion in sugar-feeding male mosquitoes suggests that this may be a pre-adaptation to blood-feeding.

The gut anti-complement activity of Aedes aegypti: Investigating new ways to control the major human arboviruses vector in the Americas.

Aedes aegypti is the main urban vector of dengue virus, chikungunya virus and Zika virus due to its great dispersal capacity and virus susceptibility. A. aegypti feed on plant-derived sugars but females need a blood meal for egg maturation. Haematophagous arthropods need to overcome host haemostasis and local immune reactions in order to take a blood meal. In this context, molecules present in the saliva and/or intestinal contents of these arthropods must contain inhibitors of the complement system (CS). CS salivary and/or intestinal inhibitors are crucial to protect gut cells of haematophagous arthropods against complement attack. The present work aimed to investigate the anti-complement activity of A. aegypti intestinal contents on the alternative, classical and lectin pathways of the human complement system. Here we show that A. aegypti gut contents inhibited the human classical and the lectin pathways but not the alternative pathway. The A. aegypti gut content has a serine protease able to specifically cleave and inactivate human C4, which is a novel mechanism for human complement inactivation in haematophagous arthropods. The gut of female A. aegypti was capable of capturing human serum factor H (a negative complement modulator), unlike males. C3 molecules in recently blood-fed female A. aegypti remain in their original state, being inactivated to iC3b soon after a blood feed. A transmission-blocking vaccine using these complement inhibitory proteins as antigens has the potential to interfere with the insect's survival, reproductive fitness and block their infection by the arboviruses they transmit to humans.