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

Abstract

BackgroundIL-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.ResultsOur 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.ConclusionTherefore, 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.Electronic supplementary materialThe online version of this article (10.1186/s12865-018-0269-5) contains supplementary material, which is available to authorized users.

The role of Toll-like receptor 9 in a murine model of Cryptococcus gattii infection

“…In a model of infection by C. neoformans (B3501 strain) in C57BL/6 IL-17-deficient mice, the role of this cytokine in controlling the disease was identified 35 , mainly due to the activity modulator of GXM. It has also been described www.nature.com/scientificreports/ that, in a model of infection by C. neoformans, a greater infiltration of Th17 lymphocytes was observed in the lungs of C57BL/6 mice, as well as an increased amount of IL-17 in this tissue 57 . Our results show that TLR9deficient mice infected with C. gattii produce less IL-17 in the lungs compared to infected WT mice (Fig.…”

Cryptococcus neoformans CAP10 Gene Regulates the Immune Response in Mice

“…Th17 cells also play an important role in infectious disease through their secreted molecules. Th17 cells and its secreted cytokines IL-17 are responsible for the immune surveillance, but also involved in the pathogenesis of many autoimmune diseases and in the mechanisms of fibrosis in many organs after the infection [21][22][23] . Unlike Th17 cells, Treg cells are a subset of T cells with immunosuppressive effects, which control the intensity of immune responses and reduce the damage of inflammatory responses to tissues 24 .…”

Cryptococcus neoformans Csn1201 Is Associated With Pulmonary Immune Responses and Disseminated Infection

“…On the other hand, the CSN1201 deletion induced significant upregulation of Th1 cytokines (IFN-γ and IL-12) and inflammatory cytokines (TNF-α and IL-17). These upregulated cytokines are essential for protective immunity against C. neoformans infection ( 22 , 35 – 37 ). Of the aforementioned cytokines, IFN-γ is probably crucial for the csn1201Δ -induced protective immune responses.…”