Gram-negative bacterial infection causes aggravated innate immune response in sepsis: Studies from clinical samples and cellular models

Abstract

Bacterial infection is the most common cause for sepsis. The purpose of this study was to evaluate the impact of different bacterial infection on sepsis based on human samples and cellular experiments. Physiological indexes and prognostic information of 121 sepsis patients were analysed based on whether they had a gram-positive or gram-negative bacterial infection. Moreover, murine RAW264.7 macrophages were treated with lipopolysaccharide (LPS) or peptidoglycan (PG) to simulate infection with gram-negative or gram-positive bacteria in sepsis, respectively. Exosomes derived from the macrophages were extracted for transcriptome sequencing. In patients with sepsis, most gram-positive bacterial infections were Staphylococcus aureus, and gram-negative infections were Escherichia coli. Gram-negative bacterial infection was significantly associated with high neutrophil and interleukin (IL)-6 levels in blood and shorter prothrombin (PT) and activated partial thromboplastin time (APTT). Intriguingly, the survival prognosis of sepsis patients was not affected by the type of bacterial infection, but it was significantly related to fibrinogen. Protein transcriptome sequencing of the macrophage-derived exosomes showed that differentially expressed proteins were significantly enriched in megakaryocyte differentiation, leukocyte and lymphocyte-mediated immunity, and complement and coagulation cascade pathways. The complement and coagulation-related proteins were significantly upregulated after LPS induction, which explained the shortened PT and APTT in gram-negative bacterial sepsis. Bacterial infection did not affect mortality in sepsis but did alter the host response. The immune disorder induced by gram-negative infection was more severe than that produced by gram-positive infection. This study provides references for the rapid identification and molecular research of different bacterial infections in sepsis.