Interleukin-17A Secreted from the Lung–infiltrating T Helper 17 Cells Renders Protective Immunity to PulmonaryCryptococcus neoformansInfection

Abstract

16IL-17A has emerged as a key player in the pathologies of inflammation, autoimmune disease, 17 and immunity to microbes since its discovery two decades ago. In this study, we aim to elucidate 18 the activity of IL-17A in the protection against Cryptococcus neoformans, an opportunistic 19 fungus that causes fatal meningoencephalitis among AIDS patients. For this purpose, we 20 examined if C. neoformans infection triggers IL-17A secretion in the in vitro setting using 21 RAW264.7 murine macrophage cells, and in vivo using wildtype C57BL/6 mice. In addition, an 22 enhanced green fluorescence protein (eGFP) reporter and a knockout (KO) mouse models were 23 used to track the source of IL-17A secretion and explore the protective function of IL-17A, 24 respectively. Our findings showed that both in vivo and in vitro models of C. neoformans 25 infection demonstrated induction of abundant IL-17A secretion. By examining the lung 26 bronchoalveolar lavage fluid (BALF), mediastinal lymph node (mLN) and spleen of the IL-17A-27 EGFP reporter mice, we showed that intranasal inoculation with C. neoformans promoted 28 leukocytes lung infiltration. A large proportion (~50%) of the infiltrated CD4 + helper T cell 29 population secreted EGFP, indicating vigorous T H 17 activity in the C. neoformans-infected lung.30