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

• Published in: BMC immunology 2018-11, Vol.19 (1), p.32-32, Article 32
• Main Authors: Movahed, Elaheh, Cheok, Yi Ying, Tan, Grace Min Yi, Lee, Chalystha Yie Qin, Cheong, Heng Choon, Velayuthan, Rukumani Devi, Tay, Sun Tee, Chong, Pei Pei, Wong, Won Fen, Looi, Chung Yeng
• Format: Article
• Language: English
• Subjects: Animal models; Autoimmune diseases; Bronchus; CD4 antigen; CD4 lymphocytes; CD4+ T cells; Cryptococcosis; Cryptococcus neoformans; Cytokines; Development and progression; Fungal infections; Health aspects; Helper cells; Host-bacteria relationships; IL-17A; Immunity (Physiology); Immunologic research; Inoculation; Interleukin-17; Leukocytes; Lungs; Lymph nodes; Lymphocytes; Lymphocytes T; Macrophages; Meningoencephalitis; Neutrophils; Respiratory tract infections; Rodents; Spleen; TH17 cells; Virulence
• ISSN: 1471-2172; 1471-2172
• DOI: 10.1186/s12865-018-0269-5

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. 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 T 17 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 is released predominantly from T 17 cells in vivo, which plays a supporting role in the protective immunity against C. neoformans infection.