Transurethral instillation with fusion protein MrpH.FimH induces protective innate immune responses against uropathogenic Escherichia coli and Proteus mirabilis

Mehri Habibi; Mohammad Reza Asadi Karam; Saeid Bouzari

doi:10.1111/apm.12523

journal article Feb 26, 2016

Transurethral instillation with fusion protein MrpH.FimH induces protective innate immune responses against uropathogenic Escherichia coli and Proteus mirabilis

Mehri Habibi Mohammad Reza Asadi Karam Saeid Bouzari

APMIS Vol. 124 No. 6 pp. 444-452 · Wiley

View at Publisher Save 10.1111/apm.12523

Abstract

Urinary tract infections (UTIs) are among the most common infections in human. Innate immunity recognizes pathogen‐associated molecular patterns (PAMPs) by Toll‐like receptors (TLRs) to activate responses against pathogens. Recently, we demonstrated that MrpH.FimH fusion protein consisting of MrpH from Proteus mirabilis and FimH from Uropathogenic Escherichia coli (UPEC) results in the higher immunogenicity and protection, as compared with FimH and MrpH alone. In this study, we evaluated the innate immunity and adjuvant properties induced by fusion MrpH.FimH through in vitro and in vivo methods. FimH and MrpH.FimH were able to induce significantly higher IL‐8 and IL‐6 responses than untreated or MrpH alone in cell lines tested. The neutrophil count was significantly higher in the fusion group than other groups. After 6 h, IL‐8 and IL‐6 production reached a peak, with a significant decline at 24 h post‐instillation in both bladder and kidney tissues. Mice instilled with the fusion and challenged with UPEC or P. mirabilis showed a significant decrease in the number of bacteria in bladder and kidney compared to control mice. The results of these studies demonstrate that the use of recombinant fusion protein encoding TLR‐4 ligand represents an effective vaccination strategy that does not require the use of a commercial adjuvant. Furthermore, MrpH.FimH was presented as a promising vaccine candidate against UTIs caused by UPEC and P. mirabilis.

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Details

Published: Feb 26, 2016
Vol/Issue: 124(6)
Pages: 444-452
License: View

Authors

M

Mehri Habibi

Department of Molecular Biology Pasteur Institute of Iran Tehran Iran

M

Mohammad Reza Asadi Karam

Department of Molecular Biology Pasteur Institute of Iran Tehran Iran

S

Saeid Bouzari

Department of Molecular Biology Pasteur Institute of Iran Tehran Iran

Funding

Pasteur Institute of Iran

Cite This Article

Mehri Habibi, Mohammad Reza Asadi Karam, Saeid Bouzari (2016). Transurethral instillation with fusion protein MrpH.FimH induces protective innate immune responses against uropathogenic Escherichia coli and Proteus mirabilis. APMIS, 124(6), 444-452. https://doi.org/10.1111/apm.12523

Transurethral instillation with fusion protein MrpH.FimH induces protective innate immune responses against uropathogenic Escherichia coli and Proteus mirabilis

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