Beneficial Effects of CpG-Oligodeoxynucleotide Treatment on Trauma and Secondary Lung Infection

Abstract

Although Streptococcus pneumoniae is usually found as a commensal in healthy individuals, it can act as a pathogen in trauma patients, causing such complications as early-onset pneumonia and sepsis. We discovered that treating mice with an A-class CpG-oligodeoxynucleotide (ODN) at 2 h after traumatic injury significantly improved mouse survival following early-onset secondary lung infection with S. pneumoniae. This study used mass cytometry (cytometry by time-of-flight) and Luminex technologies to characterize the cellular immune response to secondary S. pneumoniae lung infection at 1 and 3 d postinfection. We found increased expression of CD14, CD64, and PD-L1 on F4-80+ and F4-80+CD11c+ macrophages, CD11c+ dendritic cells, and CD14+CD172a+ cells after burn-injury and infection, supporting previous reports of innate immune cell activation in sepsis. CpG-ODN treatment at 2 h after burn-injury reversed these effects; improved pathogen clearance; and led to an increased expression of CD25, CD27, MHCII, and IL-17 on or in TCRγδ cells at 1 d postinfection. At 3 d postinfection, CpG-ODN treatment increased the expression of PD-L1 on innate cell subsets. Furthermore, we analyzed cytokine levels in lung-washout samples of TCRγδ cell–depleted (TCRγδ−) mice to demonstrate that the effects of CpG-ODN on cytokine expression after burn-injury and S. pneumoniae infection rely on functional TCRγδ cells. In summary, we demonstrate that cytometry by time-of-flight provides an effective strategy to systematically identify specific cellular phenotypic responses to trauma and bacterial pneumonia and to discover changes in immune system phenotypes associated with beneficial immunotherapy.