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The effect of YakA deficiency in T. marneffei infection of THP-1 and J774 macrophage cell lines

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2018, Master of Science in Biological Sciences, Youngstown State University, Department of Biological Sciences and Chemistry.
The goal of this study was to examine the host cytokine response to a mutant strain (ΔyakA) of T. marneffei. T. marneffei is a fungus that causes the disease talaromycosis in AIDS patients. The fungus is dimorphic and switches between growth forms depending upon temperature. T. marneffei exhibits mold growth at 25°C but transforms into yeast cells inside of the host which become intracellular pathogens, living inside a variety of cells including macrophages. Previously, our laboratory discovered a mutant, designated ΔyakA. The protein encoded by the yakA gene is a type of molecular sensor. Studies showed that the ΔyakA mutant of T. marneffei has a weakened cell wall, which may affect its pathogenicity. Therefore, conidia of the ΔyakA mutant were co-cultured with the human monocyte cell line THP-1 or the macrophage-like murine cell line J774 to investigate whether the weakened cell wall has an effect on cytokine production, since cytokines play a vital role in host response to infection. The levels of the pro-inflammatory cytokines TNF-α , IL-1β and IL-6 were measured from cell lines infected with the ΔyakA and wild-type conidia. The THP-1 human macrophages produced significantly more IL-6 and TNF-α when co-cultured with WT compared with ΔyakA but IL-1β showed no significant difference. There were no significant differences in cytokines measured from J774 mouse macrophages exposed to WT versus mutant conidia. Although some differences were noted between cytokine levels of macrophages incubated with WT versus ΔyakA conidia, the differences were not uniform enough to presently conclude that the yakA gene affects host cytokine response.
Chester Cooper, PhD (Advisor)
Diana Fagan, PhD (Committee Member)
Gary Walker, PhD (Committee Member)
Jonathan Caguiat, PhD (Committee Member)
56 p.

Recommended Citations

Citations

  • Parr, K. (2018). The effect of YakA deficiency in T. marneffei infection of THP-1 and J774 macrophage cell lines [Master's thesis, Youngstown State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ysu1534339507791902

    APA Style (7th edition)

  • Parr, Kayla. The effect of YakA deficiency in T. marneffei infection of THP-1 and J774 macrophage cell lines. 2018. Youngstown State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ysu1534339507791902.

    MLA Style (8th edition)

  • Parr, Kayla. " The effect of YakA deficiency in T. marneffei infection of THP-1 and J774 macrophage cell lines." Master's thesis, Youngstown State University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=ysu1534339507791902

    Chicago Manual of Style (17th edition)