Damage-Induced Cell Regeneration in the Midgut of Aedes albopictus Mosquitoes

Abstract

Mosquito-transmitted diseases cause over one million deaths every year. A better characterization of the vector’s physiology and immunity should provide valuable knowledge for the elaboration of control strategies. Mosquitoes depend on their innate immunity to defend themselves against pathogens. These pathogens are acquired mainly through the oral route, which places the insects’ gut at the front line of the battle. Indeed, the epithelium of the mosquito gut plays important roles against invading pathogens acting as a physical barrier, activating local defenses and triggering the systemic immune response. Therefore, the gut is constantly confronted to stress and often suffers cellular damage. In this study, we show that dividing cells exist in the digestive tract of adult A. albopictus and that these cells proliferate in the midgut after bacterial or chemical damage. An increased transcription of signaling molecules that regulate the EGFR and JAK/STAT pathways was also observed, suggesting a possible involvement of these pathways in the regeneration of damaged guts. This work provides evidence for the presence of regenerative cells in the mosquito guts, and paves the way towards a molecular and cellular characterization of the processes required to maintain mosquito’s midgut homeostasis in both normal and infectious conditions.

Comparative Analysis of Midgut Regeneration Capacity and Resistance to Oral Infection in Three Disease-Vector Mosquitoes

“…Immunohistochemistry was then performed using anti-phospho-histone H3 protein antibodies (anti-PH3), a specific marker of mitotic cells 29,30 . Similarly to what we previously reported for A. albopictus 25 , we observed a number of small cells with clear PH3 signal in the midguts of control C. pipiens midguts (Fig. 2A,D).…”

“…Adult females of the three mosquito species were starved for two hours before being allowed to feed either on sucrose (control), sucrose supplemented with Serratia marcescens , or sucrose supplemented with Sodium Dodecyl Sulfate (SDS) to induce gut damage 25–28 . Mosquito guts were dissected 24 hours post-treatment and fixed.…”

“…The old reports were based on morphological characteristics and include a study of gut wound healing in Aedes aegypti and a study that revealed the presence of proliferating cells in the guts of Culex tarsalis after blood ingestion 21–24 . More recently, we have shown that chemical damage or bacterial infections lead to regenerative cell proliferation in the midgut of adult A. albopictus 25 . A similar analysis revealed the presence of adult intestinal stem cells in A. aegypti 26 .…”

Regulation of midgut cell proliferation impacts Aedes aegypti susceptibility to dengue virus

“…In the fruit fly, the ingestion of cytotoxic agents, such as dextran sodium sulfate (DSS), bleomycin or paraquat, or infection by pathogenic bacteria can stimulates cell turnover, increasing the midgut ISC mitotic index [ 18 , 22 ]. Similar to that, it has been recently shown that cell damage produced by ingestion of several stressors also induced intestinal cell proliferation in sugar-fed Aedes albopictus [ 23 ]. Likewise, viral infections can trigger cellular responses, such as apoptosis or autophagy, in different infection models [ 24 – 27 ].…”

How are arbovirus vectors able to tolerate infection?

“…Paradoxically, inhibiting apoptosis through silencing of the initiator caspase Aedronc decreased Dengue virus load and dissemination (Eng et al, 2016) and activating apoptosis using RNAimediated silencing of the anti-apoptotic gene iap1 increased Sindbis infection (Wang et al, 2012). To compensate for the loss of apoptotic cells that could compromise tissue integrity, damage caused by chemical or infectious insults trigger an adaptive response leading to cell regeneration and reestablishment of midgut homeostasis (Janeh et al, 2017). In the context of Dengue infection, the proliferation of intestinal stem cells (ISC) is delayed in susceptible A. aegypti Rockefeller strain, suggesting that midgut cell renewal may regulate vector competence (Taracena et al, 2018).…”