The PD-1/PD-L1 pathway is induced during Borrelia burgdorferi infection and inhibits T cell joint infiltration without... 2022 Helble et al

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

Abstract
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.

Author summary
Lyme disease is caused by the bacterial pathogen Borrelia burgdorferi which can establish a long-term infection inside its mammalian hosts. One hallmark of other long-term infections is the presence of T cells that express immunoinhibitory molecules, such as PD-1. Here, we sought to characterize if the PD-1/PD-L1 pathway was upregulated during murine B. burgdorferi infection and to understand its role in the outcome of infection. We demonstrated that the PD-1/PD-L1 pathway is enriched following B. burgdorferi infection and while PD-1-/- mice do not exhibit a reduction in bacterial load compared to wild-type controls, they do exhibit an increased influx of T cells to the tissues following infection without affecting the B cell response. Our study suggests that the PD-1/PD-L1 pathway represents a key checkpoint to T cell expansion and tissue infiltration during Lyme disease.

Open access, https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1010903