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01.12.2014 | Research | Ausgabe 1/2014 Open Access

Journal of Neuroinflammation 1/2014

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

Zeitschrift:
Journal of Neuroinflammation > Ausgabe 1/2014
Autoren:
Sandra Ribes, Tanja Meister, Martina Ott, Sandra Redlich, Hana Janova, Uwe-Karsten Hanisch, Stefan Nessler, Roland Nau
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1742-2094-11-14) contains supplementary material, which is available to authorized users.

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

SRi and RN designed the study, analyzed the data, interpreted the results, and prepared the manuscript. TM, MO, SRe, and HJ performed experiments and acquired the data. SN analyzed the FACs data and discussed the manuscript. UKH reviewed and discussed the manuscript. All authors have read and approved the final version of the manuscript.

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.
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