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Infection and Immunity, November 2008, p. 5139-5148, Vol. 76, No. 11
0019-9567/08/$08.00+0     doi:10.1128/IAI.00895-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Pertussis Toxin Inhibits Early Chemokine Production To Delay Neutrophil Recruitment in Response to Bordetella pertussis Respiratory Tract Infection in Mice{triangledown}

Charlotte Andreasen{dagger} and Nicholas H. Carbonetti*

Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland

Received 21 July 2008/ Returned for modification 19 August 2008/ Accepted 27 August 2008

Pertussis is an acute respiratory disease of humans caused by the bacterium Bordetella pertussis. Pertussis toxin (PT) plays a major role in the virulence of this pathogen, including important effects that it has soon after inoculation. Studies in our laboratory and other laboratories have indicated that PT inhibits early neutrophil influx to the lungs and airways in response to B. pertussis respiratory tract infection in mice. Previous in vitro and in vivo studies have shown that PT can affect neutrophils directly by ADP ribosylating Gi proteins associated with surface chemokine receptors, thereby inhibiting neutrophil migration in response to chemokines. However, in this study, by comparing responses to wild-type (WT) and PT-deficient strains, we found that PT has an indirect inhibitory effect on neutrophil recruitment to the airways in response to infection. Analysis of lung chemokine expression indicated that PT suppresses early neutrophil recruitment by inhibiting chemokine upregulation in alveolar macrophages and other lung cells in response to B. pertussis infection. Enhancement of early neutrophil recruitment to the airways in response to WT infection by addition of exogenous keratinocyte-derived chemokine, one of the dominant neutrophil-attracting chemokines in mice, further revealed an indirect effect of PT on neutrophil chemotaxis. Additionally, we showed that intranasal administration of PT inhibits lipopolysaccharide-induced chemokine gene expression and neutrophil recruitment to the airways, presumably by modulation of signaling through Toll-like receptor 4. Collectively, these results demonstrate how PT inhibits early inflammatory responses in the respiratory tract, which reduces neutrophil influx in response to B. pertussis infection, potentially providing an advantage to the pathogen in this interaction.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, University of Maryland School of Medicine, 660 W. Redwood St., HH 324, Baltimore, MD 21201. Phone: (410) 706-7677. Fax: (410) 706-2129. E-mail: ncarbone{at}umaryland.edu

{triangledown} Published ahead of print on 2 September 2008.

Editor: R. P. Morrison

{dagger} Present address: Section of Pulmonary and Critical Care Medicine, Yale University School of Medicine, New Haven, CT.

Infection and Immunity, November 2008, p. 5139-5148, Vol. 76, No. 11
0019-9567/08/$08.00+0     doi:10.1128/IAI.00895-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Andreasen, C., Carbonetti, N. H. (2009). Role of Neutrophils in Response to Bordetella pertussis Infection in Mice. Infect. Immun. 77: 1182-1188 [Abstract] [Full Text]  


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