TY - JOUR
T1 - Single-cell transcriptome analysis of the early immune response in the lymph nodes of Borrelia burgdorferi-infected mice
AU - Rinne, Varpu
AU - Gröndahl-Yli-Hannuksela, Kirsi
AU - Fair-Mäkelä, Ruth
AU - Salmi, Marko
AU - Rantakari, Pia
AU - Lönnberg, Tapio
AU - Alinikula, Jukka
AU - Pietikäinen, Annukka
AU - Hytönen, Jukka
N1 - Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.
PY - 2025/2
Y1 - 2025/2
N2 - Lyme borreliosis is a disease caused by Borrelia burgdorferi sensu lato bacteria. Borrelia burgdorferi is known to induce prolonged extrafollicular immune responses and abnormal germinal centre formation. The infection fails to generate a neutralizing type of immunity, eventually establishing a persistent infection. Here, we performed single-cell RNA sequencing to characterize the immune landscape of lymph node lymphocytes during the early Borrelia burgdorferi infection in a murine model. Our results indicate key features of an extrafollicular immune response four days after Borrelia burgdorferi infection, including notable B cell proliferation, immunoglobulin class switching to IgG3 and IgG2b isotypes, plasmablast differentiation, and the presence of extrafollicular B cells identified through immunohistochemistry. Additionally, we found infection-derived upregulation of suppressor of cytokine signalling genes Socs1 and Socs3, along with downregulation of genes associated with MHC II antigen presentation in B cells. Our results support the central role of B cells in the immune response of a Borrelia burgdorferi infection, and provide cues of mechanisms behind the determination between extrafollicular and germinal centre responses during Borrelia burgdorferi infection.
AB - Lyme borreliosis is a disease caused by Borrelia burgdorferi sensu lato bacteria. Borrelia burgdorferi is known to induce prolonged extrafollicular immune responses and abnormal germinal centre formation. The infection fails to generate a neutralizing type of immunity, eventually establishing a persistent infection. Here, we performed single-cell RNA sequencing to characterize the immune landscape of lymph node lymphocytes during the early Borrelia burgdorferi infection in a murine model. Our results indicate key features of an extrafollicular immune response four days after Borrelia burgdorferi infection, including notable B cell proliferation, immunoglobulin class switching to IgG3 and IgG2b isotypes, plasmablast differentiation, and the presence of extrafollicular B cells identified through immunohistochemistry. Additionally, we found infection-derived upregulation of suppressor of cytokine signalling genes Socs1 and Socs3, along with downregulation of genes associated with MHC II antigen presentation in B cells. Our results support the central role of B cells in the immune response of a Borrelia burgdorferi infection, and provide cues of mechanisms behind the determination between extrafollicular and germinal centre responses during Borrelia burgdorferi infection.
KW - Single-cell RNA sequencing
KW - Murine model
KW - Lymphocyte
KW - Extrafollicular immune response
KW - Borrelia burgdorferi
U2 - 10.1016/j.micinf.2024.105424
DO - 10.1016/j.micinf.2024.105424
M3 - Article
C2 - 39306236
SN - 1286-4579
VL - 27
JO - Microbes and Infection
JF - Microbes and Infection
IS - 2
M1 - 105424
ER -