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Open Access Highly Accessed Research article

Innate immune properties of selected human neuropeptides against Moraxella catarrhalis and nontypeable Haemophilus influenzae

Daria Augustyniak1*, Adam Jankowski12, Paweł Mackiewicz3, Agnieszka Skowyra1, Jan Gutowicz4 and Zuzanna Drulis-Kawa1

Author Affiliations

1 Department of Pathogen Biology and Immunology, Institute of Genetics and Microbiology, University of Wroclaw, Przybyszewskiego 63/77, 51-148, Wroclaw, Poland

2 Department and Clinics of Pediatrics, Immunology and Rheumatology of Developmental Age, Medical University of Wroclaw, Kasprowicza 64/66, 51-137, Wroclaw, Poland

3 Department of Genomics, Faculty of Biotechnology, University of Wroclaw, Przybyszewskiego 63/77, 51-148, Wroclaw, Poland

4 Depertment of Physico-Chemistry of Microorganisms, Institute of Genetics and Microbiology, University of Wroclaw, Przybyszewskiego 63/77, 51-148, Wroclaw, Poland

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BMC Immunology 2012, 13:24  doi:10.1186/1471-2172-13-24

Published: 2 May 2012

Abstract

Background

Considerable evidence supports the concept of active communication between the nervous and immune systems. One class of such communicators are the neuropeptides (NPs). Recent reports have highlighted the antimicrobial activity of neuropeptides, placing them among the integral components of innate immune defense. This study examined the action of four human neuropeptides: calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY), substance P (SP) and somatostatin (SOM), which are accessible in the upper respiratory tract, against two human-specific respiratory pathogens. We studied: (i) neuropeptide-mediated direct antibacterial activity exerted against Moraxella catarrhalis and nontypeable Haemophilus influenzae, and (ii) indirect immunomodulatory role of these neuropeptides in the neutrophil-mediated phagocytosis of indicated pathogens.

Results

We found that 100 micromolar concentrations of CGRP, NPY, SP, and SOM effectively permeabilized bacterial membranes and showed (except SOM) bactericidal activity against both pathogens. SOM acted only bacteriostatically. However the killing efficacy was dependent on the bactericidal assay used. The rank order of killing NP effect was: NPY ≥ CGRP > SP >> SOM and correlated with their potency to permeabilize bacterial membranes. The killing and permeabilization activity of the analyzed NPs showed significant correlation with several physicochemical properties and amino acid composition of the neuropeptides. M. catarrhalis was more sensitive to neuropeptides than nontypeable H. influenzae.

The immunomodulatory bimodal effect of physiological concentrations of CGRP, NPY, and SP on the phagocytic function of human neutrophils against M. catarrhalis and H. influenzae was observed both in the ingestion (pathogen uptake) and reactive oxygen species generation stages. This effect was also dependent on the distinct type of pathogen recognition (opsonic versus nonopsonic).

Conclusions

The present results indicate that neuropeptides such as CGRP, NPY, and SP can effectively participate in the direct and indirect elimination of human-specific respiratory pathogens. Because the studied NPs show both direct and indirect modulating antimicrobial potency, they seem to be important molecules involved in the innate host defense against M. catarrhalis and nontypeable H. influenzae.

Keywords:
Neuropeptide Y; Substance P; CGRP; Somatostatin; Killing; Permeabilization; Phagocytosis; Immunomodulation; Moraxella catarrhalis; Haemophilus influenzae