PD-1 negatively tunes macrophage immune activation by turning off JNK and STAT1 signaling: Exploited by Leishmania for its intra-macrophage survival

Cell Immunol. 2023 Aug 22;391-392:104758. doi: 10.1016/j.cellimm.2023.104758. Online ahead of print.ABSTRACTThe anti-inflammatory role of the programmed death-1 receptor (PD-1) is well appreciated. However, the mechanism of how PD-1 signaling inhibits the pro-inflammatory cytokine responses in macrophages, which is further exploited by Leishmania to foster their intracellular survival, was unknown. We found that among three major MAP kinases regulating immune activation, PD-1 signaling decreased only JNK phosphorylation without perturbing p38 and ERK. Inflammatory transcription factor STAT1 was also inhibited by PD-1. Association studies documented that SHP, the downstream phosphatase of PD-1, is directly responsible for the decreased phosphorylation of JNK and STAT1. JNK and STAT1 deactivation led to Elk-1/c-Fos inhibition, which significantly decreased IL-12 and TNF-α levels. Further investigation revealed c-Fos deactivation ultimately rendered transcription factor AP1 inactive and facilitating parasite-favorable anti-inflammatory environment.PMID:37651886 | DOI:10.1016/j.cellimm.2023.104758

Source: Cellular Immunology - August 31, 2023 Category: Allergy & Immunology Authors: Shalini Roy Anand K Gupta Madhurima Banerjee Pijush K Das Anindita Ukil Source Type: research