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

Abstract

ABSTRACTIL-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 againstCryptococcus neoformans, an opportunistic fungus that causes fatal meningoencephalitis among AIDS patients. For this purpose, we examined ifC. neoformansinfection triggers IL-17A secretion in thein vitrosetting using RAW264.7 murine macrophage cells, andin vivousing 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 bothin vivoandin vitromodels ofC. neoformansinfection 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 withC. neoformanspromoted leukocytes lung infiltration. A large proportion (~50%) of the infiltrated CD4+helper T cell population secreted EGFP, indicating vigorous TH17 activity in theC. 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 cellsin vivo, is essential in providing a protective immunity againstC. neoformansinfection.