B cell immune response to human bocaviruses

Abstract

<p><strong>Background: </strong>Human bocaviruses (HBoVs) have been demonstrated in respiratory and gastrointestinal infections; however, the immune response to them has not been studied in detail. In this study, we investigated the B cell immune responses to HBoV1 and HBoV2, representing two different species of bocaviruses in humans.</p><p><strong>Methods: </strong>We analyzed the effects of stimulations with HBoV1 and 2 virus-like particles (VLPs) and of co-stimulation with HBoV1-rhinovirus (RV) on cells of the immune system by flow cytometry, transcriptomics, and luminometric immune assays.</p><p><strong>Results: </strong>Human B cells, and particularly B regulatory cells (Breg cells), showed an increased immune response to HBoV1-VLPs stimulation. These immune responses were also supported by increased IL-1RA and PDL1 expressions in IL-10⁺ B cells from peripheral blood mononuclear cells (PBMCs) stimulated with HBoV1-VLPs. In addition, increased levels of IL-10 and IL-1RA were determined in the supernatants of PBMCs following HBoV1-VLPs stimulation. HBoV1-VLPs and RV co-stimulation increased the IL-10⁺ B cell population. Transcriptome analysis by next-generation RNA sequencing showed an increased expression of IL-10 signalling and Breg cell markers in PBMCs stimulated with HBoV1-VLPs. Furthermore, TGF-β and chemoattractants MIP-1α, MIP-1β and IP10 protein levels were high in the supernatants of PBMCs stimulated with HBoV1-VLPs.</p><p><strong>Conclusions: </strong>The findings demonstrate that in Breg cells, IL-10 signalling pathways, and anti-inflammatory activity are induced by HBoV1, which can explain the often mild nature of the disease. In addition, the immune regulatory response induced by HBoV1-VLPs may indicate a potential immunomodulatory role of HBoV1 on the immune system and may represent an immune regulatory strategy.</p>