The PD-1/PD-L1 pathway is induced during Borrelia burgdorferi infection and inhibits T cell joint infiltration without compromising bacterial clearance

• Published in: PLoS pathogens Vol. 18; no. 10; p. e1010903
• Main Authors: Helble, Jennifer D, McCarthy, Julie E, Sawden, Machlan, Starnbach, Michael N, Hu, Linden T
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01-10-2022; Public Library of Science (PLoS)
• Subjects: Animal diseases; Animal models; Animals; Ankle; Antibodies; Antigen-presenting cells; Antigens; Apoptosis; Arthritis; B7-H1 Antigen; Bacteria; Biology and Life Sciences; Bone marrow; Borrelia burgdorferi; CD4 antigen; CD4-Positive T-Lymphocytes; Chemical properties; Clearances; Damage prevention; Dendritic cells; Effector cells; Expansion joints; Experiments; Flow cytometry; Health aspects; Immune system; Infections; Inflammation; Ligands (Biochemistry); Lyme disease; Lyme Disease - microbiology; Lymph nodes; Lymphatic system; Lymphocytes; Lymphocytes T; Mammals; Medicine and Health Sciences; Mice; Pathogens; PD-1 protein; PD-L1 protein; Physiological aspects; Populations; Programmed Cell Death 1 Receptor; Research and Analysis Methods; T cell receptors; T cells; Variance analysis; Vector-borne diseases; United States
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1010903

The Lyme disease bacterial pathogen, Borrelia burgdorferi, establishes a long-term infection inside its mammalian hosts. Despite the continued presence of the bacteria in animal models of disease, inflammation is transitory and resolves spontaneously. T cells with limited effector functions and the inability to become activated by antigen, termed exhausted T cells, are present in many long-term infections. These exhausted T cells mediate a balance between pathogen clearance and preventing tissue damage resulting from excess inflammation. Exhausted T cells express a variety of immunoinhibitory molecules, including the molecule PD-1. Following B. burgdorferi infection, we found that PD-1 and its ligand PD-L1 are significantly upregulated on CD4+ T cells and antigen presenting cell subsets, respectively. Using mice deficient in PD-1, we found that the PD-1/PD-L1 pathway did not impact bacterial clearance but did impact T cell expansion and accumulation in the ankle joint and popliteal lymph nodes without affecting B cell populations or antibody production, suggesting that the PD-1/PD-L1 pathway may play a role in shaping the T cell populations present in affected tissues.