Infection-Induced Interaction between the Mosquito Circulatory and Immune Systems

Abstract

Insects counter infection with innate immune responses that rely on cells called hemocytes. Hemocytes exist in association with the insect's open circulatory system and this mode of existence has likely influenced the organization and control of anti-pathogen immune responses. Previous studies reported that pathogens in the mosquito body cavity (hemocoel) accumulate on the surface of the heart. Using novel cell staining, microdissection and intravital imaging techniques, we investigated the mechanism of pathogen accumulation in the pericardium of the malaria mosquito, Anopheles gambiae, and discovered a novel insect immune tissue, herein named periostial hemocytes, that sequesters pathogens as they flow with the hemolymph. Specifically, we show that there are two types of endocytic cells that flank the heart: periostial hemocytes and pericardial cells. Resident periostial hemocytes engage in the rapid phagocytosis of pathogens, and during the course of a bacterial or Plasmodium infection, circulating hemocytes migrate to the periostial regions where they bind the cardiac musculature and each other, and continue the phagocytosis of invaders. Periostial hemocyte aggregation occurs in a time- and infection dose-dependent manner, and once this immune process is triggered, the number of periostial hemocytes remains elevated for the lifetime of the mosquito. Finally, the soluble immune elicitors peptidoglycan and β-1,3-glucan also induce periostial hemocyte aggregation, indicating that this is a generalized and basal immune response that is induced by diverse immune stimuli. These data describe a novel insect cellular immune response that fundamentally relies on the physiological interaction between the insect circulatory and immune systems.

CCAP and FMRFamide-like peptides accelerate the contraction rate of the antennal accessory pulsatile organs (auxiliary hearts) of mosquitoes

“…Contractions of the heart were counted manually by annotating each wave-like contraction of cardiac muscle that shifted the fluorescent microspheres that had aggregated at the periostial regions of the heart (King and Hillyer, 2012;Boppana and Hillyer, 2014). For CCAP, six independent trials were conducted, each containing between three and five mosquitoes per treatment (n=27 for both CCAP and PBS).…”

Blood feeding induces hemocyte proliferation and activation in the African malaria mosquito, Anopheles gambiae Giles

“…hemocytes are recruited to the midgut and dorsal vessel during Plasmodium sp. infection (Volz et al, 2005;Rodrigues et al, 2010;King and Hillyer, 2012), and may mediate innate 'immune memory' (Rodrigues et al, 2010). However, despite the multi-faceted contribution of mosquito hemocytes to immunity against malaria parasites, little is known about their basic biology.…”

“…Some mosquito hemocytes circulate freely in the hemocoel (Hall, 1983), while others are attached to a variety of tissues including midgut, trachea, muscles, dorsal vessel, Malpighian tubules, cephalic limbs and maxillary palps (Barillas-Mury et al, 1999;Danielli et al, 2000;King and Hillyer, 2012;King and Hillyer, 2013). While true cell lineages have yet to be established, mosquito hemocytes are classified based on morphological and functional characteristics.…”

“…In contrast, infection with the rodent malaria parasite Plasmodium berghei Fain does not affect overall hemocyte number (Baton et al, 2009), but induces a number of changes. These include a relative increase in granulocytes compared with oenocytoids and prohemocytes (Baton et al, 2009;Rodrigues et al, 2010), TEP1 secretion (Frolet et al, 2006), changes in lectin binding (Rodrigues et al, 2010), changes in expression patterns (Pinto et al, 2009), and hemocyte aggregation near the ostia of the dorsal vessel of the mosquito (King and Hillyer, 2012). In the absence of infection, some studies show a blood meal induces an increase in circulating hemocyte numbers in A. gambiae and A.…”

Detecting proliferation of adult hemocytes in Drosophila by BrdU incorporation

“…In vertebrates, such threat is tackled by different type of blood cells that get routinely regenerated. Studies on adult mosquito, on the other hand reveals that indeed hemocytes can proliferate upon bacterial infection to increase their number ( King & Hillyer, 2012; Sigle & Hillyer, 2016). This raised the possibility that may be this is true for Drosophila adult too.…”