Severe H7N9 Infection Is Associated with Decreased Antigen-Presenting Capacity of CD14+ Cells

Hongyan Diao,Zhigang Tian,Yu Chen,Jianing Chen,Jian Zuo,Guangying Cui,Lanjuan Li,Hangping Yao,Yingfeng Wei,Hongcui Cao,Xia Jin

doi:10.1371/journal.pone.0092823

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.

Highlights

The avian influenza A (H7N9) virus was first reported to cause human infection in eastern China in 2013
The H7N9 infected patients generally presented with severe symptoms, some patients recovered from this disease, while others experienced steady deterioration or even death [5,18]
To clarify the factors affecting the outcome of H7N9 infection, we limited the focus of our study to the immune status of confirmed H7N9 patients

Summary

Introduction

The avian influenza A (H7N9) virus was first reported to cause human infection in eastern China in 2013. With the exception of those caused by the H5N1 [2] and H7N7 [3] subtypes, Avian influenza virus (AIVs) infections were generally presented with mild manifestations such as conjunctivitis and upper-respiratory-tract infections [4]. The virus and host immune status are primary factors which influence the consequences of virus infection. These factors are not mutually exclusive, and it is conceivable that both contribute to the complex pathogenesis of viruses. CD8+ T cells, operating either via direct lysis of infected cells or by the production of pro-inflammatory cytokines such as IFN-c, are critical for the efficient resolution of influenza virus infections in animal models

Methods

Results

Conclusion