CpG oligodeoxyribonucleotides protect mice from Burkholderia pseudomallei but not Francisella tularensis Schu S4 aerosols

Abstract

Studies have shown that CpG oligodeoxyribonucleotides (ODN) protect mice from various bacterial pathogens, including Burkholderia pseudomallei and Francisella tularensis live vaccine strain (LVS), when administered before parenteral challenge. Given the potential to develop CpG ODN as a pre-treatment for multiple bacterial biological warfare agents, we examined survival, histopathology, and cytokine data from CpG ODN-treated C57BL/6 mice to determine whether previously-reported protection extended to aerosolized B. pseudomallei 1026b and highly virulent F. tularensis Schu S4 infections. We found that, although CpG ODN protected mice from aerosolized B. pseudomallei challenges, the immunostimulant failed to benefit the animals exposed to F. tularensis Schu S4 aerosols. Our results, which contrast with earlier F. tularensis LVS studies, highlight potential differences in Francisella species pathogenesis and underscore the need to evaluate immunotherapies against human pathogenic species.

Intranasal Prophylaxis with CpG Oligodeoxynucleotide Can Protect against Yersinia pestis Infection

“…Unlike the Y. pestis KIM D27 data reported here, however, CpG ODN treatment exacerbated disease in the Salmonella-infected mice, resulting in greater mortality (34). Conversely, treatment of mice with CpG ODN reduces lung bacterial burden and improves survival during lethal respiratory infections with K. pneumoniae and B. pseudomallei (25,31,32,59). Therefore, our KIM D27 plague model appears to be unique in that CpG ODN treatment increases the pulmonary bacterial burden while simultaneously promoting the survival of the host.…”

FTT0831c/FTL_0325 Contributes to Francisella tularensis Cell Division, Maintenance of Cell Shape, and Structural Integrity

“…infection (18). Other studies have shown that prior administration of known TLR agonists reduces overall organ burdens and increases survival following subsequent F. tularensis infection (46)(47)(48). However, other properties likely also contribute to the limited systemic replication of the ⌬0831 bacteria, since the Schu S4 ⌬0831 strain also failed to replicate in the spleens and livers of mice when administered systemically via i.p.…”

Targeting the “Cytokine Storm” for Therapeutic Benefit

“…However, it should be noted that such treatments are not universally successful. For example, recent studies have demonstrated that a preexposure CpG treatment strategy failed to protect mice that were subsequently infected with the highly virulent F. tularensis strain SchuS4 (46). Furthermore, there are no reported data on the efficacy of CpG treatment given postexposure against highly virulent pathogens.…”