Lung–infiltrating T helper 17 cells as the major source of interleukin-17A production during pulmonary Cryptococcus neoformans infection

Movahed, Elaheh and Cheok, Yi Ying and Tan, Grace Min Yi and Lee, Chalystha Yie Qin and Cheong, Heng Choon and Velayuthan, Rukumani Devi and Tay, Sun Tee and Chong, Pei Pei and Wong, Won Fen and Looi, Chung Yeng (2018) Lung–infiltrating T helper 17 cells as the major source of interleukin-17A production during pulmonary Cryptococcus neoformans infection. BMC Immunology, 19 (1). p. 32. ISSN 1471-2172, DOI https://doi.org/10.1186/s12865-018-0269-5.

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Official URL: https://doi.org/10.1186/s12865-018-0269-5

Abstract

Background: 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 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. Results: Our findings showed that in vivo model 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. Conclusion: Therefore, our data suggest that IL-17A is released predominantly from TH17 cells in vivo, which plays a supporting role in the protective immunity against C. neoformans infection.

Item Type: Article
Funders: Institut Mérieux – Malaysian Society of Infectious Diseases and Chemotherapy: MSIDC (IF039–2017), University of Malaya Research Grant (RG525-13HTM)
Uncontrolled Keywords: CD4+ T cells; Cryptococcus neoformans; IL-17A; Macrophages; TH17 cells
Subjects: R Medicine
Divisions: Faculty of Medicine
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 13 May 2019 04:51
Last Modified: 13 May 2019 04:51
URI: http://eprints.um.edu.my/id/eprint/21214

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