Plasmodium berghei induced priming in Anopheles albimanus independently of bacterial co-infection

Abstract

Priming in invertebrates is the acquired capacity to better combat a pathogen due to a previous exposure to sub-lethal doses of the same organism. It is proposed to be functionally analogous to immune memory in vertebrates. Previous studies with Anopheles gambiae mosquitoes provide evidence that the inhibitory response to a second challenge by the malaria parasite Plasmodium berghei resulted from a sustained activation of hemocytes by midgut bacteria. These bacteria probably accessed the hemolymph during a first aborted infection through lesions produced by parasites invading the midgut. Since the mosquito immune responses to midgut bacteria and Plasmodium overlap, it is difficult to determine the priming responses of each. We herein document priming induced in the aseptic An. albimanus midgut by P. berghei, probably independent of the immune response induced by midgut bacteria. This idea is further evidenced by experiments with Pbs 25-28 knock out parasites (having an impaired capacity for invading the mosquito midgut) and dead ookinetes. Priming protection against a homologous challenge with P. berghei lasted up to 12 days. There was greater incorporation of 5-bromo-2'-deoxyuridine into midgut cell nuclei (indicative of DNA synthesis without mitosis) and increased transcription of hnt (a gene required for the endocycle of midgut cells) in primed versus unprimed mosquitoes, suggesting that endoreplication was the underlying mechanism of priming. Moreover, the transcription of hnt and antimicrobial peptides related to an anti-Plasmodium response (attacin, cecropin and gambicin) was enhanced in a biphasic rather than sustained response after priming An. albimanus with P. berghei.

Insect immunology and hematopoiesis

“…Protection is sometimes specific to the pathogen already encountered (Pham et al, 2007; Roth et al, 2009; Sadd and Schmid-Hempel, 2006). Most often, however, protection is conferred against other pathogens as well, or protection from re-infection with the same pathogen is clearly established but the specificity of the protection remains unknown (Contreras-Garduno et al, 2015; Moret and Siva-Jothy, 2003; Rodrigues et al, 2010). The length of the protection may last the lifetime of the insect (although most of these studies have been performed in short-lived insects), or may last only for only a few days (Moret and Siva-Jothy, 2003; Pham et al, 2007).…”

Plasmodium yoelii nigeriensis (N67) Is a Robust Animal Model to Study Malaria Transmission by South American Anopheline Mosquitoes

“…berghei ANKA 2.34 strain can effectively infect An . albimanus when mosquitoes are fed ookinetes cultured in vitro , and a high prevalence (>90%) and intensity of infection (20–30 oocysts/midgut) can be obtained [19]. Multiple times we attempted to infect females from a An .…”

“…albimanus can be infected by direct feeding on P . berghei -infected mice [19] but, in general, infections are much lower when compared to An . gambiae or An .…”

Methylation on RNA: A Potential Mechanism Related to Immune Priming within But Not across Generations

“…In both vertebrates and invertebrates, acetylation is important during immune responses and resistance (reviewed in Field et al, 2004; Mukherjee et al, 2012) and a recent and interesting study suggests that miRNAs could play a key role in immune priming across generations (Mukherjee and Vilcinskas, 2014). Endoreplication is another potential mechanism because it has been implicated in immune priming within generations (Contreras-Garduño et al, 2015). Although correlative, our work suggests that the mechanism involving specific or general RNA methylation merits further research to understand the mechanisms of immune priming.…”

“…As mentioned above, the molecular basis underlying immune priming within and across generations remains poorly understood (Brehélin and Roch, 2008; Rodrigues et al, 2010; Pope et al, 2011; Mikonranta et al, 2014; Contreras-Garduño et al, 2015; Tate and Graham, 2015); but DNA methylation has been proposed as cornerstone (Jokela, 2010; Ottaviani, 2015). However, experimental evidence of differential epigenetic mechanisms of immune priming is lacking, both within and across generations (Eggert et al, 2014; Norouzitallab et al, 2015; Ottaviani, 2015).…”