Experimental Determination of the Force of Malaria Infection Reveals a Non-Linear Relationship to Mosquito Sporozoite Loads

Aleshnick, Maya; Ganusov, Vitaly V.; Nasir, Gibran; Yenokyan, Gayane; Sinnis, Photini

doi:10.1101/830299

Cited by 14 publications

(18 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Experiments in which the bite site was removed, transplanted to naïve animals, or artificially heated, and in vivo visualization of the process of sporozoite inoculation, all support the notion that the majority of sporozoites are inoculated into the skin [56][57][58][59][60][61]. This is further supported by a recent study demonstrating that bloodmeal acquisition is not associated with a higher rate of infection [62]. Due to the length of the mosquito's stylet the majority of sporozoites are inoculated into the dermis and a small proportion into the epidermis or subcutaneous tissue [63].…”

Section: Mosquito Blood-feeding Physiology and Sporozoite Inoculationmentioning

confidence: 61%

When Is a Plasmodium-Infected Mosquito an Infectious Mosquito?

Graumans¹,

Jacobs

Bousema

et al. 2020

Trends in Parasitology

Self Cite

View full text Add to dashboard Cite

The discrepancy between exposure to infected mosquito bites and malaria incidence suggests a transmission bottleneck that is currently understudied.Recent studies from non-human malaria models are indicative of a minimum salivary gland sporozoite density that is required to achieve infection following a mosquito bite.Infection-induced alterations in bloodfeeding behavior of mosquitoes may influence natural transmission dynamics.

show abstract

Section: Mosquito Blood-feeding Physiology and Sporozoite Inoculationmentioning

confidence: 61%

When Is a Plasmodium-Infected Mosquito an Infectious Mosquito?

Graumans¹,

Jacobs

Bousema

et al. 2020

Trends in Parasitology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Another apicomplexan parasite Plasmodium , the causative agents of malaria infects the liver following inoculation of parasites by probing mosquitoes 14,15 . At this stage of the lifecycle the intra-cellular liver stage parasites are susceptible to clearance by vaccine-induced CD8 T cells.…”

Section: Introduction and Resultsmentioning

confidence: 99%

Liver environment-imposed constraints diversify movement strategies of liver-localized CD8 T cells

Rajakaruna

O’Connor

Cockburn

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

Pathogen-specific CD8 T cells face the problem of finding rare cells that present their cognate antigen either in the lymph node or infected tissue. To optimize the search for rare targets it has been proposed that T cells might perform a random walk with long displacements called Levy walks enabling superdiffusive behavior and shorter search times1–3. Many agents ranging from cells to large animals have been found to perform Levy walks3–5 suggesting that Levy walk-based search strategies may be evolutionary selected6,7. However, whether random walk patterns are driven by agent-intrinsic programs or shaped by environmental factors remains largely unknown8. To address this problem we examined the behavior of activated CD8 T cells in the liver where both the movement of the cells and the underlying structural constraints can be clearly defined. We show that Plasmodium-specific liver-localized CD8 T cells perform short displacement, Brownian-like walks and yet display superdiffusive overall displacement, the cardinal feature of efficient Levy walks. Because liver-localized CD8 T cells are mainly associated with liver sinusoids, simulations of Brownian or Levy walkers in structures derived from the liver sinusoids illustrate that structure alone can enforce superdiffusive movement. Moreover, Brownian walkers require less time to find a rare target when T cells search for the infection in physiologically-derived liver structures. Importantly, analysis of fibroblastic reticular cell networks on which CD8 T cells move in lymph nodes also allows for superdiffusion in simulations, though this is not observed experimentally, suggesting that structure is not the only factor determining movement patterns of T cells. Our results strongly suggest that observed patterns of movement of CD8 T cells are likely to result from a combination of cell-intrinsic movement programs, physical constraints imposed by the environmental structures, and other environmental cues. Future work needs to focus on quantifying the relative contributions of these factors to the overall observed movement patterns of biological agents.

show abstract

“…Although the number of sporozoites in salivary glands decreased significantly, they were able to infect a new host. This is likely because even in the absence of kinesin-5, the sporozoite inoculum, number of mosquito bites, or the sporozoite infectivity to liver cells are sufficient to cause infection ( Aleshnick et al., 2020 ; Graumans et al., 2020 ). Thus, more broadly, the absence of kinesin-5 does not completely block the transmission of parasite.…”

Section: Discussionmentioning

confidence: 99%

Plasmodium berghei Kinesin-5 Associates With the Spindle Apparatus During Cell Division and Is Important for Efficient Production of Infectious Sporozoites

Zeeshan

Brady

Stanway

et al. 2020

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

Kinesin-5 motors play essential roles in spindle apparatus assembly during cell division, by generating forces to establish and maintain the spindle bipolarity essential for proper chromosome segregation. Kinesin-5 is largely conserved structurally and functionally in model eukaryotes, but its role is unknown in the Plasmodium parasite, an evolutionarily divergent organism with several atypical features of both mitotic and meiotic cell division. We have investigated the function and subcellular location of kinesin-5 during cell division throughout the Plasmodium berghei life cycle. Deletion of kinesin-5 had little visible effect at any proliferative stage except sporozoite production in oocysts, resulting in a significant decrease in the number of motile sporozoites in mosquito salivary glands, which were able to infect a new vertebrate host. Live-cell imaging showed kinesin-5-GFP located on the spindle and at spindle poles during both atypical mitosis and meiosis. Fixed-cell immunofluorescence assays revealed kinesin-5 co-localized with α-tubulin and centrin-2 and a partial overlap with kinetochore marker NDC80 during early blood stage schizogony. Dual-color live-cell imaging showed that kinesin-5 is closely associated with NDC80 during male gametogony, but not with kinesin-8B, a marker of the basal body and axonemes of the forming flagella. Treatment of gametocytes with microtubule-specific inhibitors confirmed kinesin-5 association with nuclear spindles and not cytoplasmic axonemal microtubules. Altogether, our results demonstrate that kinesin-5 is associated with the spindle apparatus, expressed in proliferating parasite stages, and important for efficient production of infectious sporozoites.

show abstract

Experimental Determination of the Force of Malaria Infection Reveals a Non-Linear Relationship to Mosquito Sporozoite Loads

Cited by 14 publications

References 57 publications

When Is a Plasmodium-Infected Mosquito an Infectious Mosquito?

When Is a Plasmodium-Infected Mosquito an Infectious Mosquito?

Liver environment-imposed constraints diversify movement strategies of liver-localized CD8 T cells

Plasmodium berghei Kinesin-5 Associates With the Spindle Apparatus During Cell Division and Is Important for Efficient Production of Infectious Sporozoites

Contact Info

Product

Resources

About