Role of Natural Killer Cells in Chronic Toxoplasma gondii Infection

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Presentation transcript:

Role of Natural Killer Cells in Chronic Toxoplasma gondii Infection Ryan Krempels and Dr. Jason Gigley

Toxoplasma gondii Obligate intracellular parasite. Generally asymptomatic in healthy individuals. Up to 60 million Americans infected. 2nd largest cause of death from food borne illness. cdc.gov Taylor J. Sulerud

Persistent life long infection Immunocompetent Persistent life long infection Behavioral changes, Dementia, Alzheimer’s Immunocompromised Toxoplasmic encephalitis (TE) Death. Fetal transmission Blindness, Hydrocephaly, Birth Defects, Spontaneous abortion. http://dna.kdna.ucla.edu/parasite_course-old/toxo_files/subchapters/life%20cycle.htm

The Immune System http://www.cancer.gov/cancertopics/pdq/treatment/CLL/Patient/page1#figure_153_e

NK Cells Innate immunity during acute infection. Cytotoxicity T-cell activation Recently shown to provide a memory immune response. Cooper et al. Gigley et al.

Specific Aims Aim 1: Demonstrate that NK cells play a role in controlling chronic T. gondii infection Aim 2: Determine the functionality of NK cells during chronic T. gondii infection

There is no change in the number of NK cells in the spleen of chronically infected mice. CD4 CD49b CD8 CD8 A. CD4 CD49b Week Wee 7 CD8 CD8

IFNγ expression decreases during T. gondii reactivation. CD49b IFNγ

CD107a expression increases during T. gondii reactivation. CD49b CD107a

PD-1 is upregulated in infected mice but does not change between weeks five and seven post infection. WK 5 WK7 Add legend

NK cells maintain their ability to proliferate after chronic infection.

An increased number of NK cells express CD107a when rechallenged five weeks after initial infection, but fewer NK cells express CD107a when rechallenged after seven weeks of infection. A. B. *

IFNγ expression increases significantly upon rechallenge with T. gondii

Consistent depletion of NK cells during chronic T Consistent depletion of NK cells during chronic T. gondii infection results in improved survival.

Inconsistent depletion of NK cells leads to no change in survival.

Conclusions NK cells negatively impact survival in chronically infected mice. NK cells switch from immunostimulatory to cytotoxic function during chronic infection.

Future Directions Address the Mechanism of NK cell contribution to reactivation of T. gondii. Determine if NK cells are targeting and killing T-cells during chronic infection.

References Prevention, CDC-Centers for Disease Control and. “CDC - Toxoplasmosis - General Information.” Accessed April 30, 2015. http://www.cdc.gov/parasites/toxoplasmosis/gen_info/index.html. Cooper, Megan A., Marco Colonna, and Wayne M. Yokoyama. “Hidden Talents of Natural Killers: NK Cells in Innate and Adaptive Immunity.” EMBO Reports 10, no. 10 (October 2009): 1103–10. doi:10.1038/embor.2009.203. Gigley, Jason P., Rajarshi Bhadra, Magali M. Moretto, and Imtiaz A. Khan. “T Cell Exhaustion in Protozoan Disease.” Trends in Parasitology 28, no. 9 (September 2012): 377–84. doi:10.1016/j.pt.2012.07.001.