Laminin and the malaria parasite's journey through the mosquito midgut

Abstract

During the invasion of the mosquito midgut epithelium, Plasmodium ookinetes come to rest on the basal lamina, where they transform into the sporozoite-producing oocysts. Laminin, one of the basal lamina's major components, has previously been shown to bind several surface proteins of Plasmodium ookinetes. Here, using the recently developed RNAi technique in mosquitoes, we used a specific dsRNA construct targeted against the LANB2 gene (laminin γ1) of Anopheles gambiae to reduce its mRNA levels, leading to a substantial reduction in the number of successfully developed oocysts in the mosquito midgut. Moreover, this molecular relationship is corroborated by the intimate association of developing P. berghei parasites and laminin in the gut, as observed using confocal microscopy. Our data support the notion of laminin playing a functional role in the development of the malaria parasite within the mosquito midgut.

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

“…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). AgMMP1 could mask the parasite from mosquito immune attacks, as has been suggested for laminin (76) and other molecules of the ECM, such as collagen (77). Additionally, the protease could process effector molecules of the innate immune system, such as antimicrobial peptides (78,79) and the complement C3-like protein TEP1 (thioester-containing protein 1) (80), a very potent effector against bacteria and/or P. berghei.…”

Plasmodium Oocysts: Overlooked Targets of Mosquito Immunity

“…The contact with components of the midgut basal lamina (collagen and laminin) is thought to trigger the differentiation of ookinetes into oocysts [18,19], but it is unclear how this interaction initiates the developmental progression into an oocyst stage (Table 1). Furthermore, several ookinete surface proteins have been shown to specifically interact with mosquito laminin, including P25/28, circumsporozoite-and TRAP-related protein (CTRP), and secreted ookinete adhesive protein (SOAP) [19].…”

“…Furthermore, several ookinete surface proteins have been shown to specifically interact with mosquito laminin, including P25/28, circumsporozoite-and TRAP-related protein (CTRP), and secreted ookinete adhesive protein (SOAP) [19]. Additional experiments in which gametocytes or ookinetes survive and produce mature oocysts when injected into the hemocoel of either mosquitoes [20][21][22] or Drosophila [23,24] indicate that ookinete invasion is not an essential step for progression into the oocyst stage.…”

“…In addition, the components of the oocyst capsule have been shown to vary during oocyst development. For example, mosquito laminin and the parasite protein Cap380 are incorporated early into the developing Plasmodium berghei oocyst and remain throughout development [19,28] (Figure 2). By contrast, early oocysts retain the ookinete surface markers P25/28 on the oocyst capsule until it is internalized for degradation or shed; the capsule is completely absent by day 6 post-infection [28] (Figure 2).…”

Toward Silencing the Burden of Malaria: Progress and Prospects for RNAi-based Approaches

“…A recent RNAi study, for example, has revealed a crucial role for mosquito laminin in this process. RNAi-targeting of this gene resulted in loss of basal lamina integrity that decreased oocyst numbers by approximately 60% (18). Most recent RNAi studies, however, have targeted mosquito immune genes to unravel their role in parasite development.…”