Establishment of an in vitro model of monocyte-like THP-1 cells for trained immunity induced by bacillus Calmette-Guérin

• Published in: BMC microbiology Vol. 24; no. 1; pp. 130 - 10
• Main Authors: Xu, Jin-Chuan, Wu, Kang, Ma, Rui-qing, Li, Jian-hui, Tao, Jie, Hu, Zhidong, Fan, Xiao-Yong
• Format: Journal Article
• Language: English
• Published: London BioMed Central 20.04.2024; BioMed Central Ltd; BMC
• Subjects: 1-Phosphatidylinositol 3-kinase; Acetic acid; AKT protein; Analysis; Antigens; Bacillus Calmette-Guerin vaccine; Bacillus Calmette-Guérin (BCG); Bacteria; BCG; BCG vaccines; Biological Microscopy; Biomedical and Life Sciences; Cell differentiation; Cell viability; Chemokines; CXCL10 protein; Cytokines; Diagnosis; Dosage and administration; Drug therapy; Genes; HIV; Human immunodeficiency virus; Immunity; Infections; Inflammation; Leukocytes; Leukocytes (neutrophilic); Life Sciences; Lipopolysaccharides; Macrophages; MAP kinase; Metabolism; Microbiology; Monocyte; Monocytes; Mycology; Neutrophils; NF-κB protein; Parasitology; Pathogens; Patient outcomes; Phagocytes; Phorbol 12-myristate 13-acetate; Signal transduction; THP-1; TOR protein; Trained immunity; Transcriptomics; Tuberculosis; Virology; China; THP-1; Bacillus Calmette-Guérin (BCG); Trained immunity; Monocyte
• ISSN: 1471-2180; 1471-2180
• DOI: 10.1186/s12866-024-03191-x

Background Mycobacteria bloodstream infections are common in immunocompromised people and usually have disastrous consequences. As the primary phagocytes in the bloodstream, monocytes and neutrophils play critical roles in the fight against bloodstream mycobacteria infections. In contrast to macrophages, the responses of monocytes infected with the mycobacteria have been less investigated. Results In this study, we first established a protocol for infection of non-adherent monocyte-like THP-1 cells (i.e. without the differentiation induced by phorbol 12-myristate 13-acetate (PMA) by bacillus Calmette-Guérin (BCG). Via the protocol, we were then capable of exploring the global transcriptomic profiles of non-adherent THP-1 cells infected with BCG, and found that NF-κB, MAPK and PI3K-Akt signaling pathways were enhanced, as well as some inflammatory chemokine/cytokine genes ( e.g. CCL4 , CXCL10 , TNF and IL-1β ) were up-regulated. Surprisingly, the Akt-HIF-mTOR signaling pathway was also activated, which induces trained immunity. In this in vitro infection model, increased cytokine responses to lipopolysaccharides (LPS) restimulation, higher cell viability, and decreased Candida albicans loads were observed. Conclusions We have first characterized the transcriptomic profiles of BCG-infected non-adherent THP-1 cells, and first developed a trained immunity in vitro model of the cells.