Mosquito Infection Responses to Developing Filarial Worms

Abstract

Human lymphatic filariasis is a mosquito-vectored disease caused by the nematode parasites Wuchereria bancrofti, Brugia malayi and Brugia timori. These are relatively large roundworms that can cause considerable damage in compatible mosquito vectors. In order to assess how mosquitoes respond to infection in compatible mosquito-filarial worm associations, microarray analysis was used to evaluate transcriptome changes in Aedes aegypti at various times during B. malayi development. Changes in transcript abundance in response to the different stages of B. malayi infection were diverse. At the early stages of midgut and thoracic muscle cell penetration, a greater number of genes were repressed compared to those that were induced (20 vs. 8). The non-feeding, intracellular first-stage larvae elicited few differences, with 4 transcripts showing an increased and 9 a decreased abundance relative to controls. Several cecropin transcripts increased in abundance after parasites molted to second-stage larvae. However, the greatest number of transcripts changed in abundance after larvae molted to third-stage larvae and migrated to the head and proboscis (120 induced, 38 repressed), including a large number of putative, immunity-related genes (∼13% of genes with predicted functions). To test whether the innate immune system of mosquitoes was capable of modulating permissiveness to the parasite, we activated the Toll and Imd pathway controlled rel family transcription factors Rel1 and Rel2 (by RNA interference knockdown of the pathway's negative regulators Cactus and Caspar) during the early stages of infection with B. malayi. The activation of either of these immune signaling pathways, or knockdown of the Toll pathway, did not affect B. malayi in Ae. aegypti. The possibility of LF parasites evading mosquito immune responses during successful development is discussed.

Vector competence of Aedes aegypti mosquitoes for filarial nematodes is affected by age and nutrient limitation

“…We measured the parasite load of all live females on either the 10 th or 11 th days post infection, when the parasites had fully developed into L3 larvae, the infective stage (Erickson et al, 2009). We separated the thorax from the abdomen of each female using entomological blunt forceps and incubated this in 50 µl phosphate buffered saline (PBS) at 37 o C for 1 hour, which causes L3s to exit the carcass.…”

“…Malarial parasites can take from 9 to 15 days between being ingested in a blood meal to become fully developed and migrate to the mosquito's salivary glands for transmission (Warrell and Gilles, 2002). The dengue fever virus (Chan and Johansson, 2012) and filarial nematodes (Erickson et al, 2009) have similar incubation periods. For these diseases, the rate of transmission will depend on the age structure of the vector population, and this can be targeted by vector control programmes aiming to reduce transmission (Cook et al, 2008).…”

What does not kill them makes them stronger: larval environment and infectious dose alter mosquito potential to transmit filarial worms

“…Sheathed microfilariae (mf ) are ingested during a blood meal from a vertebrate host. Within hours, mf exsheath and perforate the mosquito midgut, escaping into the haemocoel [22]. mf migrate to flight muscle where they undergo two moults, each separated by 2-3 days.…”

“…The terminal stage in the mosquito (L3) typically occurs 8-9 days post-infection (DPI). L3 worms migrate to the head and proboscis where they may escape during future blood meals, infecting a new host [22]. Worms may remain in the head for the life of the mosquito [23], creating multiple opportunities for transmission.…”

The Use of Filariae as a Therapeutic Agent for Hypersensitivity Diseases

“…L3 larvae then molt to the L4 and L5 (adult) stage within the lymphatics. Adult larvae tend to prefer lymphatics located in the lower extremities, such as near the inguinal lymph nodes (45 Once inside the vector, MF penetrate the midgut and migrate to the flight wing muscles (53). They then enter a muscle cell and advance to the next larval stage (L2)…”