The changes of expressive levels of IL-17A, STAT3, and RORγt in different invasive pulmonary aspergillosis mice

Abstract

BackgroundT helper 17 (Th17) lymphocytes play an important role in Aspergillus adaptive immune response against Aspergillus fumigatus, but there is little attention focused on the different types of immunosuppressive models in which invasive pulmonary aspergillosis (IPA) develops. In addition, the expression levels of signal transducer and activator of transcription 3 (STAT3)/retinoic acid-related orphan nuclear receptor gamma (RORγt)/interleukin (IL)-17A signaling pathway, which is involved in the regulation of Th17 cells, as well as whether there are differences between two types of IPA mice models, remain unknown.Materials and methodsSix to eight weeks old female BALB/c mice were treated with cortisone acetate or cyclophosphamide to establish the immunosuppressive mice models, and then, A. fumigatus inoculum was injected to form the IPA groups and sterile saline was injected to form the control groups. Flow cytometry was performed to measure the proportion of Th17 cells in CD4+ T cells in the peripheral blood, spleen, and lung of the mice. The expression of IL-17A, RORγt, and STAT3 mRNA was detected by real-time polymerase chain reaction. Concentrations of IL-6 in the plasma and bronchoalveolar lavage fluid were measured by enzyme-linked immunosorbent assay.ResultsThe proportion of Th17 in the peripheral blood and lung tissue in neutropenic IPA mice showed a more significant increase than in non-neutropenic IPA mice (P<0.01). The IL-6 protein also showed the same trend in plasma and bronchoalveolar lavage fluid (P<0.01). Compared with the control groups, the expression of IL-17A at mRNA level in the lung was significantly increased, while RORγt/STAT3 mRNA was significantly decreased in the IPA groups (P<0.01).ConclusionThe expression of RORγt and STAT3 mRNA in the lung tissue in both groups was significantly decreased. IL-17 may play a negative role in the defense against Aspergillus through uprating IL-6.

Evaluating the Role of STAT3 in CD4 + T Cells in Susceptibility to Invasive Aspergillosis

“…In control (Stat3 fl/fl ) immunosuppressed mice, we observed elevated levels of TNF, IFN, IL-6, IL-17A in the BAL. This is consistent with what others have reported in immunosuppressed mice during IA (22). The mortality rate of 60% in control immunosuppressed mice is also compatible with what has been previously reported in the literature (23).…”

Antifungal Activity of Sodium New Houttuyfonate Against Aspergillus fumigatus in vitro and in vivo

“…In mice with IPA, excessive Th2-type reactivity has been found to be associated with poor prognosis in aspergillosis ( Cenci et al, 2000 ). Moreover, Th1 cytokines (e.g., IFN-γ and TNF) are the key components of innate and adaptive immunity in anti-aspergillus defense ( Singh et al, 2009 ; Park et al, 2009 ; Schmidt et al, 2011 ; Xu et al, 2018 ). Investigations have indicated that IFN-γ- and TNF-α- treated mice with IA show decreased mortality ( Nagai et al, 1995 ).…”

Diagnosis values of Dectin-1 and IL-17 levels in plasma for invasive pulmonary aspergillosis in bronchiectasis

“…IL-17 plays a crucial role in defence against invasive infections caused by fungal pathogens of the Aspergillus by inducing antimicrobial proteins and recruiting neutrophils to the site of infection (Puerta-Arias et al, 2020). In a study of invasive pulmonary aspergillosis mice, it was found that IL-17A mRNA expression was significantly increased in the lung tissue in the IPA group (Xu et al, 2018). Kimura et al found that IL-17 levels in bronchoalveolar lavage fluid of mice infected with Aspergillus fumigatus increased gradually as GM levels, and posaconazole treatment significantly reduced IL-17 level (Kimura et al, 2017).…”

“…IL-17 plays a crucial role in defence against invasive infections caused by fungal pathogens of the Aspergillus by inducing antimicrobial proteins and recruiting neutrophils to the site of infection ( Puerta-Arias et al., 2020 ). In a study of invasive pulmonary aspergillosis mice, it was found that IL-17A mRNA expression was significantly increased in the lung tissue in the IPA group ( Xu et al., 2018 ). Kimura et al.…”