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-induced immune suppression is a major obstacle faced by the host for controlling infections. impairment of antigen-specific T-cell responses is achieved through inhibiting the proliferation of peripheral blood mononuclear cells (PBMCs). This impairment may contribute to the persistence of infection in various sites, including lungs, and its systemic spread to various organs such as joints, with the underlying mechanisms remaining elusive. Here, we elucidated the role of the immune-inhibitory receptor programmed death 1 (PD-1) and its ligand (PD-L1) in infection. Flow cytometry (FCM) analyses revealed an upregulation of PD-L1 expression on tracheal and lung epithelial cell lines after infection. In addition, we found increased PD-L1 expression on purified lung lavage macrophages following infection by FCM and determined its localization by immunofluorescence analysis comparing infected and control lung tissue sections. Moreover, infection increased the expression of the PD-1 receptor on total PBMCs and in gated CD4 and CD8 T-cell subpopulations. We demonstrated that infection induced a significant decrease in CD4 PD-1 and CD8 PD-1 subsets with intermediate PD-1 expression, which functioned as progenitor pools giving rise to CD4 PD-1 and CD8 PD-1 subsets with high PD-1 expression levels. We blocked PD-1 receptors on PBMCs using anti-PD-1 antibody at the beginning of infection, leading to a significant restoration of the proliferation of PBMCs. Taken together, our data indicate a significant involvement of the PD-1/PD-L1 inhibitory pathway during infection and its associated immune exhaustion, culminating in impaired host immune responses.

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