Hijacking of Host Cellular Functions by an Intracellular Parasite, the Microsporidian Anncaliia algerae

Abstract

Intracellular pathogens including bacteria, viruses and protozoa hijack host cell functions to access nutrients and to bypass cellular defenses and immune responses. These strategies have been acquired through selective pressure and allowed pathogens to reach an appropriate cellular niche for their survival and growth. To get new insights on how parasites hijack host cellular functions, we developed a SILAC (Stable Isotope Labeling by Amino Acids in Cell culture) quantitative proteomics workflow. Our study focused on deciphering the cross-talk in a host-parasite association, involving human foreskin fibroblasts (HFF) and the microsporidia Anncaliia algerae, a fungus related parasite with an obligate intracellular lifestyle and a strong host dependency. The host-parasite cross-talk was analyzed at five post-infection times 1, 6, 12 and 24 hours post-infection (hpi) and 8 days post-infection (dpi). A significant up-regulation of four interferon-induced proteins with tetratricopeptide repeats IFIT1, IFIT2, IFIT3 and MX1 was observed at 8 dpi suggesting a type 1 interferon (IFN) host response. Quantitative alteration of host proteins involved in biological functions such as signaling (STAT1, Ras) and reduction of the translation activity (EIF3) confirmed a host type 1 IFN response. Interestingly, the SILAC approach also allowed the detection of 148 A. algerae proteins during the kinetics of infection. Among these proteins many are involved in parasite proliferation, and an over-representation of putative secreted effectors proteins was observed. Finally our survey also suggests that A. algerae could use a transposable element as a lure strategy to escape the host innate immune system.

Modulation of host cell SUMOylation facilitates efficient development of Plasmodium berghei and Toxoplasma gondii

“…The RNA‐binding ability of IFIT2 protein is required for antiviral activity and to promote apoptosis (Reich, ). Further, IFIT2 is also known to modulate the microtubule network implicated in cell reorganization during Anncaliia algerae infection as a host response to clear infection (Panek et al, ). The cytokines CCL5 and IL4 are part of the cascade of events leading to efficient parasite control in Leishmania major (Santiago et al, ) and Listeria (Kaufmann, Emoto, Szalay, Barsig, & Flesch, ) infections, respectively.…”

“…The RNA-binding ability of IFIT2 protein is required for antiviral activity and to promote apoptosis (Reich, 2013). Further, IFIT2 is also known to modulate the microtubule network implicated in cell reorganization during Anncaliia algerae infection as a host response to clear infection (Panek et al, 2014). The cytokines CCL5 and IL4 are part of the cascade of events leading to efficient parasite control in Leishmania major (Santiago et al, 2004) and Listeria (Kaufmann, Emoto, Szalay, Barsig, & Flesch, 1997) Our transcriptome data from P. berghei-infected HepG2 cells (Spz+), when compared to previous study of transcriptional landscape of murine hepatoma (Hepa1-6) cells infected with P. berghei sporozoites (Albuquerque et al, 2009), revealed similarity in the differential expression of several host genes such as AARS, CHAC1, DPP7, GPR137, KIF5C, KLF4, MAF, NR4A2, NRP, PROC, PTPN14, and SLC16A4.…”

A revalidation and critique of assumptions about urinary sample collection methods, specimen quality and contamination

“…The innate immune response to this microbial colonisation is increased urothelial cell shedding, which may be promoted by mast cells [41]. The shed cells may be colonised or unaffected, but the proportion of parasitised cells in the face of infection would be expected to increase [42]. This sediment, a mixture of white cells, epithelial cells and debris, is likely to collect under the influence of gravity at the bladder base, forming a sampling target that should not be influenced by dilution effects.…”

Exploiting the architecture and the features of the microsporidian genomes to investigate diversity and impact of these parasites on ecosystems

“…This in turn could occasionally yield genotypes that can jump to new host populations or even to new host species, as suggested for filamentous plant pathogens (Raffaele and Kamoun, 2012). Furthermore, recent study also suggests that A. algerae could use a TE as a lure strategy to escape the host innate immune system (Panek et al, 2014). Therefore, TEs may play an important role not solely in modulating the microsporidian genome architecture but also in the capacity of these parasites to infest multiple hosts and especially to adapt to new hosts.…”