scholarly journals Type-I IFN Signaling Suppresses an Excessive IFN-γ Response and Thus Prevents Lung Damage and Chronic Inflammation During Pneumocystis (PC) Clearance in CD4 T Cell-Competent Mice

2010 ◽  
Vol 176 (6) ◽  
pp. 2806-2818 ◽  
Author(s):  
Nicole Meissner ◽  
Steve Swain ◽  
Kate McInnerney ◽  
Soo Han ◽  
Allen G. Harmsen
2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Bo Ryeong Lee ◽  
Soo Kyung Jeong ◽  
Byung Cheol Ahn ◽  
Byeong-Jae Lee ◽  
Sung Jae Shin ◽  
...  

2014 ◽  
Vol 10 (3) ◽  
pp. e1003976 ◽  
Author(s):  
Cecile Le Saout ◽  
Rebecca B. Hasley ◽  
Hiromi Imamichi ◽  
Lueng Tcheung ◽  
Zonghui Hu ◽  
...  

2019 ◽  
Vol 15 (10) ◽  
pp. e1008060 ◽  
Author(s):  
Xavier Dagenais-Lussier ◽  
Hamza Loucif ◽  
Hugo Cadorel ◽  
Juliette Blumberger ◽  
Stéphane Isnard ◽  
...  
Keyword(s):  
T Cell ◽  
Type I ◽  

2016 ◽  
Vol 1 (1) ◽  
pp. 107 ◽  
Author(s):  
Netanya Sandler Utay ◽  
Daniel C. Douek

Whether type I interferons (IFNs) hinder or facilitate HIV disease progression is controversial. Type I IFNs induce the production of restriction factors that protect against mucosal HIV/SIV acquisition and limit virus replication once systemic infection is established. However, type I IFNs also increase systemic immune activation, a predictor of poor CD4+ T-cell recovery and progression to AIDS, and facilitate production and recruitment of target CD4+ T cells. In addition, type I IFNs induce CD4+ T-cell apoptosis and limit antigen-specific CD4+ and CD8+ T-cell responses. The outcomes of type I IFN signaling may depend on the timing of IFN-stimulated gene upregulation relative to HIV exposure and infection, local versus systemic type I IFN-stimulated gene expression, and the subtype of type I IFN evaluated. To date, most interventional studies have evaluated IFNa2 administration largely in chronic HIV infection, and few have evaluated the effects on tissues or the HIV reservoir. Thus, whether the effect of type I IFN signaling on HIV disease is good, bad, or so complicated as to be ugly remains a topic of hot debate.


2020 ◽  
Vol 28 (3) ◽  
pp. 758-770 ◽  
Author(s):  
Jamie L. Shirley ◽  
Geoffrey D. Keeler ◽  
Alexandra Sherman ◽  
Irene Zolotukhin ◽  
David M. Markusic ◽  
...  

2020 ◽  
Vol 18 (5) ◽  
pp. 354-361
Author(s):  
Gülay Okay ◽  
Meliha Meric Koc ◽  
Eray Metin Guler ◽  
Ayşegül Yabaci ◽  
Abdürrahim Kocyigit ◽  
...  

Background: Serum cytokine levels over the course of HIV infection usually increase with immunosuppression and decrease after antiretroviral treatment (ART). Objectives: The aim of the study is to compare cytokine levels between HIV-infected patients (HIP) and controls and investigate the relationship between CD4+T cell count, HIV-RNA levels, and cytokine levels. Methods: The study subjects comprised ART-naive HIP (n=30) with no comorbidities and age-and sex-matched healthy controls. We measured levels of IL-6, IL-1β, TNF-α, and IFN-γ in serum samples of HIP at the beginning and at month 6 of ART and in controls. Results: The mean age of the study subjects was 38.7 ±10.3 years, with men making up 86.7% of the study subjects (n=26). IL-6, IL-1β, and TNF-α levels were significantly higher in both ART-naive (p<0.001, p=0.002, p=0.001) and ART-experienced HIP (p<0.001) than controls. The IFN-γ level was lower in both ART-naive and ART-experienced HIP compared to controls (p=0.082 and p=0.002). There was a positive correlation between the CD4+T cell count and serum concentration of IFN- γ(r=0.320, p<0.05). While the serum IFN-γ concentration showed a negative correlation with the HIVRNA level(r=-0.412, p<0.001), the serum IL-1β, IL-6, and TNF-α concentrations showed a positive correlation with the HIV-RNA level (r=0.349, p<0.001; r:0.54, p<0.001; r:0.438, p<0.00). Conclusions: Although serum concentrations of IL-6, IL-1β and TNF-α showed a significant decrease after ART, they were still significantly higher than the controls. IFN-γ responded differently to ART compared to the other cytokines, indicating that it may play a distinct and important role in the pathogenesis of HIV infection.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Norzawani Buang ◽  
Lunnathaya Tapeng ◽  
Victor Gray ◽  
Alessandro Sardini ◽  
Chad Whilding ◽  
...  

AbstractThe majority of patients with systemic lupus erythematosus (SLE) have high expression of type I IFN-stimulated genes. Mitochondrial abnormalities have also been reported, but the contribution of type I IFN exposure to these changes is unknown. Here, we show downregulation of mitochondria-derived genes and mitochondria-associated metabolic pathways in IFN-High patients from transcriptomic analysis of CD4+ and CD8+ T cells. CD8+ T cells from these patients have enlarged mitochondria and lower spare respiratory capacity associated with increased cell death upon rechallenge with TCR stimulation. These mitochondrial abnormalities can be phenocopied by exposing CD8+ T cells from healthy volunteers to type I IFN and TCR stimulation. Mechanistically these ‘SLE-like’ conditions increase CD8+ T cell NAD+ consumption resulting in impaired mitochondrial respiration and reduced cell viability, both of which can be rectified by NAD+ supplementation. Our data suggest that type I IFN exposure contributes to SLE pathogenesis by promoting CD8+ T cell death via metabolic rewiring.


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