Research Article: Microsporidia infection impacts the host cell’s cycle and reduces host cell apoptosis

Date Published: February 2, 2017

Publisher: Public Library of Science

Author(s): Raquel Martín-Hernández, Mariano Higes, Soledad Sagastume, Ángeles Juarranz, Joyce Dias-Almeida, Giles E. Budge, Aránzazu Meana, Neil Boonham, Erjun Ling.

http://doi.org/10.1371/journal.pone.0170183

Abstract

Intracellular parasites can alter the cellular machinery of host cells to create a safe haven for their survival. In this regard, microsporidia are obligate intracellular fungal parasites with extremely reduced genomes and hence, they are strongly dependent on their host for energy and resources. To date, there are few studies into host cell manipulation by microsporidia, most of which have focused on morphological aspects. The microsporidia Nosema apis and Nosema ceranae are worldwide parasites of honey bees, infecting their ventricular epithelial cells. In this work, quantitative gene expression and histology were studied to investigate how these two parasites manipulate their host’s cells at the molecular level. Both these microsporidia provoke infection-induced regulation of genes involved in apoptosis and the cell cycle. The up-regulation of buffy (which encodes a pro-survival protein) and BIRC5 (belonging to the Inhibitor Apoptosis protein family) was observed after infection, shedding light on the pathways that these pathogens use to inhibit host cell apoptosis. Curiously, different routes related to cell cycle were modified after infection by each microsporidia. In the case of N. apis, cyclin B1, dacapo and E2F2 were up-regulated, whereas only cyclin E was up-regulated by N. ceranae, in both cases promoting the G1/S phase transition. This is the first report describing molecular pathways related to parasite-host interactions that are probably intended to ensure the parasite’s survival within the cell.

Partial Text

Parasitism is a type of biological interaction between organisms of different species whereby the parasite benefits at the expense of the host. Host cells have developed a defense machinery to resist pathogen invasion and replication. In order to limit pathogen growth, these systems include mechanism such as the fusion of phagolysosomals, the production of reactive oxygen and reactive nitrogen intermediates, nutrient sequestration or cell suicide (apoptosis) in order to limit pathogen growth [1]. As a counterpoint, obligate parasites have to exploit their host to complete the processes critical for their survival. It is interesting how some intracellular parasites can reprogram their host’s cells to create a safe haven, utilizing the cellular machinery to acquire the necessary resources [2]. The implementation of these defence systems and the ability of successful pathogens to mitigate their effects are ultimately mediated by changes in both the levels and activities of key proteins.

The success of Nosema infection (checked in the bee ampoules) was reflected by the detection of spores in each group. Consequently, all the bees were successfully infected by either N. ceranae or N. apis, while no cross-infection between groups was detected and there was no infection in the uninfected groups. However, one sample from the group A and another bee from the group CH showed a very low level of infection (Ct value > 36 in Nosema infection analysis; see above) and they were not considered for the gene expression analysis.

The natural response of an infected cell is to undergo apoptosis in order to prevent the multiplication and dissemination of the invader. Conversely, the invader must find ways to evade this to be able to reproduce [6]. In this work, microsporidia have been shown to successfully manipulate the host cell’s metabolism to progress along the parasite’s life cycle, not only modifying the expression of apoptotic genes but also other important routes implicated in the host’s cell cycle. These responses seem to offer an important advantage, because similar conclusions have been reported for many intracellular parasites [3–7, 14].

 

Source:

http://doi.org/10.1371/journal.pone.0170183

 

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