Single-cell RNA sequencing reveals the expansion of circulating tissue-homing B cell subsets in secondary acute dengue viral infection
Jantarika Kumar Arora,
Ponpan Matangkasombut,
Varodom Charoensawan,
Anunya Opasawatchai,
Anavaj Sakuntabhai,
Pratap Singhasivanon,
Swangjit Suraamornkul,
Tawatchai Yingtaweesak,
Khajohnpong Manopwisedjaroen,
Nada Pitabut
Affiliations
Jantarika Kumar Arora
Doctor of Philosophy Program in Biochemistry (International Program), Faculty of Science, Mahidol University, Bangkok, 10400, Thailand; Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand
Ponpan Matangkasombut
Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand; Single-cell Omics and Systems Biology of Diseases Research Unit, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand; Corresponding author. Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand.
Varodom Charoensawan
Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand; Single-cell Omics and Systems Biology of Diseases Research Unit, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand; Integrative Computational BioScience (ICBS) Center, Mahidol University, Nakhon Pathom, 73170, Thailand; Division of Medical Bioinformatics, Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand; Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand; Siriraj Genomics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand; School of Chemistry, Institute of Science, Suranaree University of Technology, Nakhon Ratchasima, 30000, Thailand; Corresponding author. Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand.
Anunya Opasawatchai
Single-cell Omics and Systems Biology of Diseases Research Unit, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand; Integrative Computational BioScience (ICBS) Center, Mahidol University, Nakhon Pathom, 73170, Thailand; Department of Oral Microbiology, Faculty of Dentistry, Mahidol University, Bangkok, 10400, Thailand; Corresponding author. Department of Oral Microbiology, Faculty of Dentistry, Mahidol University, Bangkok, 10400, Thailand.
Anavaj Sakuntabhai
Functional Genetics of Infectious Diseases Unit, Institut Pasteur, Paris, France; Centre National de la Recherche Scientifique (CNRS), URM2000, Paris, France
Pratap Singhasivanon
Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
Swangjit Suraamornkul
Endocrinology Division, Department of Medicine, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, Bangkok, Thailand
Tawatchai Yingtaweesak
Thasongyang Hospital, Tak, Thailand
Khajohnpong Manopwisedjaroen
Department of Microbiology, Faculty of Science, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
Nada Pitabut
Faculty of Tropical Medicine, Mahidol University, Faculty of Medicine, King Mongkut's Institute of Technology Ladkrabang, Bangkok, Thailand
The roles of antibodies secreted by subsets of B cells in dengue virus (DENV) infection have been extensively studied, yet, the contribution of tissue-homing B cells to antiviral immunity remains unclear. In this study, we performed a comprehensive analysis of B cell subpopulations in peripheral blood samples from DENV-infected patients using single-cell RNA-sequencing (scRNA-seq) datasets and flow cytometry. We showed that plasma cells (PCs) and plasmablasts (PBs) were the predominant B cell populations during the acute phase of secondary natural DENV infection, but not in convalescent phase nor in healthy controls. Interestingly, these cells expressed proliferation, adhesion, and tissue-homing genes, including SELPLG, a homing marker of the skin, the initial infected site of DENV. Flow cytometry analysis confirmed a significant upregulation of cell surface expression of a cutaneous lymphocyte-associated antigen (CLA) encoded by SELPLG in PCs and PBs, compared to naive and memory B cells from the same patients. The analysis of an independent single-cell B-cell receptor sequencing (scBCR-seq) dataset of DENV-infected patients revealed that the peripheral blood PCs and PBs exhibited the highest clonal expansion in secondary DENV infection compared to other B cell subsets. These clonally expanded cells also expressed the highest levels of tissue-homing genes, including SELPLG. In addition, by utilizing a public scRNA-seq dataset of SARS-CoV2 infection, we demonstrated the upregulation of several tissue-homing genes in PCs and PBs. Our study provides evidence for the potential roles of tissue-homing B cell subsets in the context of immune responses against viral infections in humans.
