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

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.

Increased IFN‐γ+ and TNF‐α+ mucosal‐associated invariant T cells in patients with aplastic anemia

“…The frequency of MAIT cells that produce IFN‐γ and TNF‐α was examined by intracellular staining flow cytometry (Kim et al, 2022; Ouyang et al, 2021). Freshly isolated peripheral blood mononuclear cells (PBMCs) were used for functional assays.…”

Pneumonia-Induced Inflammation, Resolution and Cardiovascular Disease: Causes, Consequences and Clinical Opportunities

“…81 Synthesis of proinflammatory signaling molecules during pneumonia increases recruitment of leukocytes to the tissue that aids in pathogen clearance. Key recruited leukocytes that play a role in antimicrobial defence are neutrophils, alveolar macrophages, recruited monocytes, dendritic cells, natural killer cells, mucosaassociated invariant T cells, T cells, and B cells, [82][83][84] in addition to epithelial cells that play an important role in regulating acute and adaptive immunity. [85][86][87] Downstream of TLR and other PRR activation, phospholipases are activated and metabolize membrane phospholipids to produce AA.…”

The Distribution of Myeloid-Derived Suppressor Cells subsets and Up-regulation of Programmed Death-1/PD-L1 axis in Peripheral Blood of Adult CAP Patients

“…Community-acquired pneumonia (CAP) is still an important infectious cause of mortality and morbidity worldwide caused by a wide variety of micro-organisms including bacteria, fungi and virus [1]. The host innate and adaptive immune responses play crucial roles in the pathological processes of CAP and determine disease severity [2][3][4]. Previous studies have demonstrated that the dysregulation of T cells, neutrophils and macrophages are involved in CAP [2][3][4].…”

“…The host innate and adaptive immune responses play crucial roles in the pathological processes of CAP and determine disease severity [2][3][4]. Previous studies have demonstrated that the dysregulation of T cells, neutrophils and macrophages are involved in CAP [2][3][4]. Recent research indicates that myeloid-derived suppressor cells (MDSCs) also play key roles in maintaining pulmonary homeostasis [5,6] and the role of MDSCs in CAP has not been fully elucidated.…”