Intraperitoneal prophylaxis with CpG oligodeoxynucleotides protects neutropenic mice against intracerebral Escherichia coli K1 infection.

Abstract

BACKGROUND:

Prophylaxis with unmethylated cytosine phosphate guanidine (CpG) oligodeoxynucleotides (ODN) protects against several systemic experimental infections. Escherichia coli is a major cause of Gram-negative neonatal bacterial meningitis and also causes meningitis and meningoencephalitis in older and immunocompromised patients.

METHODS:

Wild-type (wt) and Toll-like receptor 9 (TLR9)-deficient mice were rendered neutropenic by intraperitoneal administration of the anti-Ly-6G monoclonal antibody. Immunocompetent and neutropenic mice received intraperitoneal CpG ODN or vehicle 72 h prior to induction of E. coli K1 meningoencephalitis.

RESULTS:

Pre-treatment with CpG ODN significantly increased survival of neutropenic wt mice from 33% to 75% (P = 0.0003) but did not protect neutropenic TLR9-/- mice. The protective effect of CpG ODN was associated with an enhanced production of interleukin (IL)-12/IL-23p40 with sustained increased levels in serum and spleen at least for 17 days after conditioning compared to buffer-treated animals. CpG-treated neutropenic wt mice showed reduced bacterial concentrations and increased recruitment of Ly6ChighCCR2+ monocytes in brain and spleen 42 h after infection. The levels of macrophage inflammatory protein 1α (MIP-1α) and interferon gamma (IFN-γ) in spleen were higher 42 h after infection in CpG-treated compared to buffer-treated neutropenic animals. In immunocompetent mice, prophylaxis with CpG ODN did not significantly increase survival compared to the buffer group (60% vs. 45%, P = 0.2).

CONCLUSIONS:

These findings suggest that systemic administration of CpG ODN may help to prevent bacterial CNS infections in immunocompromised individuals.

• Authors: Sandra Ribes, Tanja Meister, Martina Ott, Sandra Redlich, Hana Janova, Uwe-Karsten Hanisch, Stefan Nessler, Roland Nau
• Journal: Journal of neuroinflammation (J Neuroinflammation) Vol. 11 Pg. 14 (Jan 23 2014) ISSN: 1742-2094 [Electronic] England
• PMID: 24456653 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD
• Cytokines
• Oligodeoxyribonucleotides
• Tlr9 protein, mouse
• Toll-Like Receptor 9
• Guanidine

Topics

• Animals
• Antigens, CD (metabolism)
• Central Nervous System (drug effects, microbiology, pathology)
• Cytokines (metabolism)
• Disease Models, Animal
• Drug Administration Schedule
• Escherichia coli (physiology)
• Escherichia coli Infections (prevention & control)
• Flow Cytometry
• Guanidine (chemistry)
• Meningoencephalitis (prevention & control)
• Mice
• Mice, Knockout
• Oligodeoxyribonucleotides (therapeutic use)
• Spleen (microbiology, pathology)
• Toll-Like Receptor 9 (deficiency)