Prokineticin 2 promotes macrophages-mediated antibacterial host defense against bacterial pneumonia

Objectives: Bacterial pneumonia is a common serious infectious disease with high morbidity and mortal-ity. Prokineticin 2 (PK2) has recently been identified as a novel immunomodulator in a variety of diseases; however, its role in bacterial pneumonia remains unclear. Methods: The levels of PK2 were measured and analyzed in patients with pneumonia and healthy con-trols. The effects of PK2 on the host response to pneumonia were evaluated by in vivo animal experiments and in vitro cell experiments.Results: PK2 levels dramatically decreased in patients with pneumonia compared with healthy controls, and PK2 levels were lower in patients with severe pneumonia than in pneumonia. In a mouse model of bacterial pneumonia, transtracheal administration of recombinant PK2 significantly alleviated lung in-jury and improved the survival, which was associated with increased host's bacterial clearance capacity, as manifested by decreased pulmonary bacterial loads. PK2 enhanced the chemotaxis, phagocytosis, and killing ability of macrophages, whereas the protective efficacy of PK2 was abolished after macrophage depletion.Conclusion: Impaired alveolar macrophage function caused by decreased PK2 is a new endogenous cause of the occurrence and development of bacterial pneumonia. The administration of recombinant PK2 may be a potential adjuvant therapy for bacterial pneumonia.& COPY; 2022 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )

Automated summary

This study investigated the role of Prokineticin 2 (PK2) in bacterial pneumonia. The levels of PK2 were found to be decreased in patients with pneumonia compared to healthy controls, and even lower in patients with severe pneumonia. Administering recombinant PK2 in a mouse model of bacterial pneumonia alleviated lung injury, improved survival, and enhanced the host's bacterial clearance capacity. PK2 was shown to enhance the chemotaxis, phagocytosis, and killing ability of macrophages.