Circulating Plasmacytoid and Conventional Dendritic Cells Are Numerically and Functionally Deficient in Patients With Scrub Typhus

Abstract

BackgroundDendritic cells (DCs) are specialized antigen-presenting cells known to bridge innate and adaptive immune reactions. However, the relationship between circulating DCs and Orientia tsutsugamushi infection is unclear. Therefore, this study aimed to examine the level and function of plasmacytoid DCs (pDCs) and conventional DCs (cDCs), two subsets of circulating DCs, in scrub typhus patients.MethodsThe study included 35 scrub typhus patients and 35 healthy controls (HCs). pDC and cDC levels, CD86 and CD274 expression, and cytokine levels were measured using flow cytometry.ResultsCirculating pDC and cDC levels were found to be significantly reduced in scrub typhus patients, which were correlated with disease severity. The patients displayed increased percentages of CD86+ pDCs, CD274+ pDCs, and CD274+ cDCs in the peripheral blood. The alterations in the levels and surface phenotypes of pDCs and cDCs were recovered in the remission state. In addition, the production of interferon (IFN)-α and tumor necrosis factor (TNF)-α by circulating pDCs, and interleukin (IL)-12 and TNF-α by circulating cDCs was reduced in scrub typhus patients. Interestingly, our in vitro experiments showed that the percentages of CD86+ pDCs, CD274+ pDCs, and CD274+ cDCs were increased in cultures treated with cytokines including IFN-γ, IL-12, and TNF-α.ConclusionsThis study demonstrates that circulating pDCs and cDCs are numerically deficient and functionally impaired in scrub typhus patients. In addition, alterations in the expression levels of surface phenotypes of pDCs and cDCs could be affected by pro-inflammatory cytokines.

Genomic bacterial load associated with bacterial genotypes and clinical characteristics in patients with scrub typhus in Hainan Island, Southern China

“…Genomic DNA was extracted from whole blood samples using a QIAamp DNA Mini Kit (QIAGEN, Hilden, Germany) according to the manufacturer’s instructions. Nested PCR was performed using primers targeting a 483bp fragment of the 56-kDa TSA gene as previously reported [ 23 ]]. The amplified product of nested PCR was purified using a QIAquick gel extraction kit (Qiagen) and sent to Sangon Biotech (Sangon, Shanghai) for Sanger sequencing with a 3730×1 DNA analyzer (Applied Biosystems, Foster, CA, USA) in both forward and reverse directions.…”

Contrariety of Human Bone Marrow Mesenchymal Stromal Cell Functionality in Modulating Circulatory Myeloid and Plasmacytoid Dendritic Cell Subsets

“…Ex vivo investigation of circulating dendritic cells taken from the peripheral blood (without manufacturing dendritic cells from monocytes) will inform the clinical relevance of MSC therapy since infused MSCs encounter cellular compartments of the peripheral blood, including dendritic cells. In addition, circulating dendritic cell frequency and functionality vary in several diseases, which also indicates its significance in systemic immune modulation [33][34][35][36]. Thus, in the present study, we aim to identify the effect of human bone-marrow-derived MSCs on circulating myeloid and plamacytoid dendritic cells upon their coculture ex vivo.…”