Biology subjects

Kumarasingha, R.

Publications and source records attributed to Kumarasingha, R..

2 recordsLinked to original sources

bioRxiv2020

Transcriptional memory-like imprints and enhanced functional activity in γδ T cells following resolution of malaria infection

{gamma}{delta} T cells play an essential role in the immune response to malaria infection. However, long-lasting effects of malaria infection on the {gamma}{delta} T cell population still remain inadequately understood. This study investigated transcriptional changes and memory-like functional capacity of malaria pre-exposed {gamma}{delta} T cells using a Plasmodium chabaudi infection model. We show that multiple genes associated with effector function (chemokines, cytokines and cytotoxicity) and antigen-presentation were upregulated in P. chabaudi-exposed {gamma}{delta} T cells compared to {gamma}{delta} T cells from naive mice. This transcriptional profile was positively correlated with profiles observed in conventional memory CD8+ T cells and was accompanied by enhanced reactivation upon secondary encounter with Plasmodium-infected red blood cells in vitro. Collectively our data demonstrate that Plasmodium exposure result in "memory-like imprints" in the {gamma}{delta} T cell population and also promotes {gamma}{delta} T cells that can support antigen-presentation during subsequent infections.

immunology↗

bioRxiv2018

Knockdown of the translocon protein EXP2, reduces growth and protein export in malaria parasites.

Malaria parasites remodel their host erythrocytes to gain nutrients and avoid the immune system. Host erythrocytes are modified by hundreds of effectors proteins exported from the parasites into the host cell. Protein export is mediated by the PTEX translocon comprising five core components of which EXP2 is considered to form the putative pore that spans the vacuole membrane enveloping the parasite within its erythrocyte. To explore the function and importance of EXP2 for parasite survival in the asexual blood stage of Plasmodium falciparum we inducibly knocked down the expression of EXP2. Reduction in EXP2 expression strongly reduced parasite growth proportional to the degree of protein knockdown and tended to stall development about half way through the asexual cell cycle. Once the knockdown inducer was removed and EXP2 expression restored, parasite growth recovered dependent upon the length and degree of knockdown. To establish EXP2 function and hence the basis for growth reduction, the trafficking of an exported protein was monitored following EXP2 knockdown. This resulted in severe attenuation of protein export and is consistent with EXP2, and PTEX in general, being the conduit for export of proteins into the host compartment.

microbiology↗