A New Role for an Old Antimicrobial: Lysozyme c-1 Can Function to Protect Malaria Parasites in Anopheles Mosquitoes

Abstract

Background Plasmodium requires an obligatory life stage in its mosquito host. The parasites encounter a number of insults while journeying through this host and have developed mechanisms to avoid host defenses. Lysozymes are a family of important antimicrobial immune effectors produced by mosquitoes in response to microbial challenge.Methodology/Principal FindingsA mosquito lysozyme was identified as a protective agonist for Plasmodium. Immunohistochemical analyses demonstrated that Anopheles gambiae lysozyme c-1 binds to oocysts of Plasmodium berghei and Plasmodium falciparum at 2 and 5 days after infection. Similar results were observed with Anopheles stephensi and P. falciparum, suggesting wide occurrence of this phenomenon across parasite and vector species. Lysozyme c-1 did not bind to cultured ookinetes nor did recombinant lysozyme c-1 affect ookinete viability. dsRNA-mediated silencing of LYSC-1 in Anopheles gambiae significantly reduced the intensity and the prevalence of Plasmodium berghei infection. We conclude that this host antibacterial protein directly interacts with and facilitates development of Plasmodium oocysts within the mosquito.Conclusions/SignificanceThis work identifies mosquito lysozyme c-1 as a positive mediator of Plasmodium development as its reduction reduces parasite load in the mosquito host. These findings improve our understanding of parasite development and provide a novel target to interrupt parasite transmission to human hosts.

Functional Characterization of Anopheles Matrix Metalloprotease 1 Reveals Its Agonistic Role during Sporogonic Development of Malaria Parasites

“…One hypothesis could be that the deposited material interacts with molecules of the mosquito immune system, thus protecting the growing oocyst, either actively or passively. A similar role was assigned to Anopheles lysozyme c-1, which also interacts with the surfaces of growing oocysts (74). It has been documented that the number of P. berghei parasites present in the midgut 24 h PF decreases gradually during the next 2 days due to immune responses (48,75).…”

On the Molecular Basis of Division of Labor in Solenopsis invicta (Hymenoptera: Formicidae) Workers: RNA-seq Analysis

“…Thus, we three samples for foragers and three for nurses were processed for RNA as mentioned above. Candidate genes we selected for qRT-PCR were found as differentially expressed in RNA-seq experiment and are known to play a role in key biological functions of model organisms (followed by published reference): odorant binding protein ‘ OBP 11 ’ (olfactory response, Forêt and Maleszka 2006), chemosensory protein ‘ CSP11 ’ (expressed in insect sensory appendages and involved in chemical signaling, González et al 2009), lysozyme c-1 (antimicrobial response, Kajla et al 2011), hymenoptaecin ‘ Hym ’ (antimicrobial peptide, Casteels et al 1993), foraging ‘ for ’ (feeding behavior and polyethism, Ingram et al 2011), synaptotagmin-1 ‘ Syt-1 ’ (neurotransmitter secretion, Brose et al 1992) and down syndrome cell adhesion molecule-like protein ‘ Dscam ’ (regulating axon configuration in mushroom bodies, Hummel et al 2003). Specific primers were designed with NCBI primer-blast for these target genes and the reference gene elongation factor 1-beta (‘ ef1-beta ’, refer to Supp Table 1 [online only]).…”

Insect immunology and hematopoiesis

“…Unlike AMPs, which are produced in response to an immune insult, lysozymes are usually present in low, constitutive levels and are transcriptionally upregulated following infection. Although lysozymes are classically active in the lytic antibacterial response (Elmogy et al, 2015; Kwon et al, 2014b), some also have anti- Plasmodium and anti-fungal activity (Kajla et al, 2011; Sowa-Jasilek et al, 2014), and can activate the phenoloxidase-based melanization pathway (Li and Paskewitz, 2006; Rao et al, 2010). In addition to being involved in immunity, some insect lysozymes are expressed in the gut and function in digestion (Ito et al, 1995; Ursic-Bedoya et al, 2008).…”