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Severe H7N9 infection is associated with decreased antigen-presenting capacity of CD14+ cells.

ABSTRACT: The outbreak of H7N9 human infection has caused concern worldwide, but the immunological characteristics of infected patients and the determinants of diverse outcomes remain to be thoroughly understood. In this study, twenty-three patients with H7N9 infections were classified into severe and mild cases. We found that severe patients were commonly lymphopenic with significantly lower levels of T cells, monocytes and related cytokine levels compared to the mild cases. The expression of HLA-DR on CD14+ cells were significantly lower in the severe infection group compared to the mild group (in acute phase: 34.65±4.88 vs. 10.37±1.69, p<0.001). Importantly, the expression of HLA-DR on CD14+ cells was negatively correlated with H7N9 infection severity. Furthermore, although the phagocytosis capabilities of monocyte were similar between two groups, the monocytes of severe infection patients had a lower antigen-presenting capacity. And some in vitro experiments suggested that the impaired antigen-presenting function is associated with lower activation of T cells in responses to immune stimulation. Our present study suggested that the severe H7N9 patients were in a state of immune decrease which presented with general lymphopenia and low antigen-presenting capacity resulting in impaired T cell response. Additionally, HLA-DR levels of CD14+ cells may be a potential biomarker for predicting H7N9 disease progression.

SUBMITTER: Diao H

PROVIDER: S-EPMC3963940 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Severe H7N9 infection is associated with decreased antigen-presenting capacity of CD14+ cells.

Diao Hongyan H Cui Guangying G Wei Yingfeng Y Chen Jianing J Zuo Jian J Cao Hongcui H Chen Yu Y Yao Hangping H Tian Zhigang Z Li Lanjuan L

PloS one 20140324 3

The outbreak of H7N9 human infection has caused concern worldwide, but the immunological characteristics of infected patients and the determinants of diverse outcomes remain to be thoroughly understood. In this study, twenty-three patients with H7N9 infections were classified into severe and mild cases. We found that severe patients were commonly lymphopenic with significantly lower levels of T cells, monocytes and related cytokine levels compared to the mild cases. The expression of HLA-DR on C ...[more]

PMID: 24664315

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Project description:BACKGROUND:Many lines of evidence suggest that accumulation of aggregated alpha-synuclein (?SYN) in the Parkinson's disease (PD) brain causes infiltration of T cells. However, in which ways the stationary brain cells interact with the T cells remain elusive. Here, we identify astrocytes as potential antigen-presenting cells capable of activating T cells in the PD brain. Astrocytes are a major component of the nervous system, and accumulating data indicate that astrocytes can play a central role during PD progression. METHODS:To investigate the role of astrocytes in antigen presentation and T-cell activation in the PD brain, we analyzed post mortem brain tissue from PD patients and controls. Moreover, we studied the capacity of cultured human astrocytes and adult human microglia to act as professional antigen-presenting cells following exposure to preformed ?SYN fibrils. RESULTS:Our analysis of post mortem brain tissue demonstrated that PD patients express high levels of MHC-II, which correlated with the load of pathological, phosphorylated ?SYN. Interestingly, a very high proportion of the MHC-II co-localized with astrocytic markers. Importantly, we found both perivascular and infiltrated CD4+ T cells to be surrounded by MHC-II expressing astrocytes, confirming an astrocyte T cell cross-talk in the PD brain. Moreover, we showed that ?SYN accumulation in cultured human astrocytes triggered surface expression of co-stimulatory molecules critical for T-cell activation, while cultured human microglia displayed very poor antigen presentation capacity. Notably, intercellular transfer of ?SYN/MHC-II deposits occurred between astrocytes via tunneling nanotubes, indicating spreading of inflammation in addition to toxic protein aggregates. CONCLUSIONS:In conclusion, our data from histology and cell culture studies suggest an important role for astrocytes in antigen presentation and T-cell activation in the PD brain, highlighting astrocytes as a promising therapeutic target in the context of chronic inflammation.

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Severe H7N9 infection is associated with decreased antigen-presenting capacity of CD14+ cells.

Publications

Severe H7N9 infection is associated with decreased antigen-presenting capacity of CD14+ cells.

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