Activation and Functional Alteration of Mucosal-Associated Invariant T Cells in Adult Patients With Community-Acquired Pneumonia.

Lichen Ouyang,Xiongwen Wu,Zhihui Liang,Muqing Yu,Xiufang Weng,Juan Zhao,Lang Jiang,Wei Wang,Yeli Gong,Zhijun Shen,Xue Cheng,Mi Wu

doi:10.3389/fimmu.2021.788406

Abstract

Community-acquired pneumonia (CAP) remains the significant infectious cause of morbidity and mortality worldwide. Although mucosal-associated invariant T cells (MAIT) play roles in the pathogenesis of children CAP and ICU-associated pneumonia, their roles in adult CAP are largely unexplored. In this study, we investigated the frequency, phenotype, and function of MAIT cells in peripheral blood and bronchoalveolar lavage fluid (BALF) of adult CAP patients. Our data indicate that MAIT-cell frequency is profoundly lower in the peripheral blood of CAP patients compared to that in healthy individuals. Furthermore, the circulatory MAIT cells express higher levels of CD69 and PD-1 compared to those in healthy individuals. In BALF of CAP patients, MAIT-cell frequency is higher and MAIT cells express higher levels of CD69 and PD-1 compared to their matched blood counterparts. Levels of IL-17A and IFN-γ are increased in BALF of CAP patients compared to those in BALF of patients with pulmonary small nodules. The IL-17A/IFN-γ ratio is significantly positively correlated with MAIT frequency in BALF of CAP patients, suggesting a pathogenic role of MAIT-17 cells in CAP. Of note, blood MAIT-cell frequency in CAP patients is strongly negatively correlated with high-sensitivity C-reactive protein (hsCRP) and neutrophil count percentage in blood. The ability of circulating MAIT cells in CAP patients to produce IFN-γ is significantly impaired compared to those in healthy individuals. In summary, our findings suggest the possible involvement of MAIT cells in the immunopathogenesis of adult CAP.

Highlights

Community-acquired pneumonia (CAP) is an important infectious cause of mortality and morbidity worldwide which is caused by a wide spectrum of microbial pathogens outside a healthcare setting including bacteria, viruses, and fungi [1]
mucosal-associated invariant T (MAIT)-cell frequencies among CD3+ T cells were significantly reduced in peripheral blood of CAP patients (p < 0.01, Figure 1A)
We found a profound decline of MAIT cells in the blood of connective tissue diseases associated interstitial lung disease (CTD-ILD) in comparison to healthy individuals (p < 0.01, Figure 1A)

Summary

Introduction

Community-acquired pneumonia (CAP) is an important infectious cause of mortality and morbidity worldwide which is caused by a wide spectrum of microbial pathogens outside a healthcare setting including bacteria, viruses, and fungi [1]. The host innate and adaptive immune responses play pivotal roles in host defense against pathogens and in determining disease severity. Previous studies have demonstrated that dysfunctional neutrophils and CD4+Th17 cells are involved in the pathogenesis of CAP [3, 4]. Recent studies suggest that unconventional T cells are equivalently important in the pathogenesis of CAP [5–7]. Unconventional innate-like T cells, including invariant NKT cells, gdT cells, and mucosal-associated invariant T (MAIT) cells, are known to bridge the innate and adaptive arms of the immune response and play key roles in maintaining pulmonary homeostasis and the integrity of the lung epithelium [8]

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