Interleukin-17A Secreted from the Lung-infiltrating T Helper 17 Cells Renders Protective Immunity to Pulmonary Cryptococcus neoformans Infection

Movahed, E.; Tan, G. M. Y.; Cheong, H. C.; Lee, C. Y. Q.; Cheok, Y. Y.; Tay, S. T.; Chong, P. P.; Wong, W. F.; Looi, C. Y.

doi:10.1101/328005

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bioRxiv · 10.1101/328005

Interleukin-17A Secreted from the Lung-infiltrating T Helper 17 Cells Renders Protective Immunity to Pulmonary Cryptococcus neoformans Infection

Movahed, E.·Tan, G. M. Y.·Cheong, H. C.·Lee, C. Y. Q.·Cheok, Y. Y.·Tay, S. T.·Chong, P. P.·Wong, W. F.·Looi, C. Y.

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Abstract

IL-17A has emerged as a key player in the pathologies of inflammation, autoimmune disease, and immunity to microbes since its discovery two decades ago. In this study, we aim to elucidate the activity of IL-17A in the protection against Cryptococcus neoformans, an opportunistic fungus that causes fatal meningoencephalitis among AIDS patients. For this purpose, we examined if C. neoformans infection triggers IL-17A secretion in the in vitro setting using RAW264.7 murine macrophage cells, and in vivo using wildtype C57BL/6 mice. In addition, an enhanced green fluorescence protein (eGFP) reporter and a knockout (KO) mouse models were used to track the source of IL-17A secretion and explore the protective function of IL-17A, respectively. Our findings showed that both in vivo and in vitro models of C. neoformans infection demonstrated induction of abundant IL-17A secretion. By examining the lung bronchoalveolar lavage fluid (BALF), mediastinal lymph node (mLN) and spleen of the IL-17A- EGFP reporter mice, we showed that intranasal inoculation with C. neoformans promoted leukocytes lung infiltration. A large proportion (~50%) of the infiltrated CD4+ helper T cell population secreted EGFP, indicating vigorous TH17 activity in the C. neoformans-infected lung. The infection study in IL-17A-KO mice, on the other hand, revealed that absence of IL-17A marginally boosted fungal burden in the lung and accelerated the mouse death. Therefore, our data suggest that IL-17A, released predominantly from TH17 cells in vivo, is essential in providing a protective immunity against C. neoformans infection.

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Movahed, E., Tan, G. M. Y., Cheong, H. C., Lee, C. Y. Q., Cheok, Y. Y., Tay, S. T., Chong, P. P., Wong, W. F., Looi, C. Y.. 2018-05-23. Interleukin-17A Secreted from the Lung-infiltrating T Helper 17 Cells Renders Protective Immunity to Pulmonary Cryptococcus neoformans Infection. https://doi.org/10.1101/328005

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