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Infection and Immunity, November 2007, p. 5361-5367, Vol. 75, No. 11
0019-9567/07/$08.00+0     doi:10.1128/IAI.02008-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Differential Contribution of Bacterial N-Formyl-Methionyl-Leucyl- Phenylalanine and Host-Derived CXC Chemokines to Neutrophil Infiltration into Pulmonary Alveoli during Murine Pneumococcal Pneumonia{triangledown}

Jean-François Gauthier, Andrée Fortin, Yves Bergeron, Marie-Christine Dumas, Marie-Eve Champagne, and Michel G. Bergeron*

Research Center for Infectious Diseases, Laval University, Quebec City, Quebec, Canada G1V 4G2

Received 22 December 2006/ Returned for modification 19 February 2007/ Accepted 11 August 2007

Despite the development of new potent antibiotics, Streptococcus pneumoniae remains the leading cause of death from bacterial pneumonia. Polymorphonuclear neutrophil (PMN) recruitment into the lungs is a primordial step towards host survival. Bacterium-derived N-formyl peptides (N-formyl-methionyl-leucyl-phenylalanine [fMLP]) and host-derived chemokines (KC and macrophage inflammatory protein 2 [MIP-2]) are likely candidates among chemoattractants to coordinate PMN infiltration into alveolar spaces. To investigate the contribution of each in the context of pneumococcal pneumonia, CD1, BALB/c, CBA/ca, C57BL/6, and formyl peptide receptor (FPR)-knockout C57BL/6 mice were infected with 106 or 107 CFU of penicillin/erythromycin-susceptible or -resistant serotype 3 or 14 S. pneumoniae strains. Antagonists to the FPR, such as cyclosporine H (CsH) and chenodeoxycholic acid, or neutralizing antibodies to KC and MIP-2 were injected either 1 h before or 30 min after infection, and then bronchoalveolar lavage fluids were obtained for quantification of bacteria, leukocytes, and chemokines. CsH was effective over a short period after infection with a high inoculum, while anti-CXC chemokine antibodies were effective after challenge with a low inoculum. CsH prevented PMN infiltration in CD1 mice infected with either serotype 3 or 14, whereas antichemokine antibodies showed better efficacy against the serotype 3 strain. When different mouse strains were challenged with serotype 3 bacteria, CsH prevented PMN migration in the CD1 mice only, whereas the antibodies were effective against CD1 and C57BL/6 mice. Our results suggest that fMLP and chemokines play important roles in pneumococcal pneumonia and that these roles vary according to bacterial and host genetic backgrounds, implying redundancy among chemoattractant molecules.

* Corresponding author. Mailing address: Division of Microbiology, Laval University, and Research Center for Infectious Diseases, CHUQ, CHUL Building, 2705 Laurier Blvd., Quebec City, Quebec, Canada G1V 4G2. Phone: (418) 654-2705. Fax: (418) 654-2715. E-mail: Michel.G.Bergeron{at}crchul.ulaval.ca

{triangledown} Published ahead of print on 20 August 2007.

Editor: A. Camilli

Infection and Immunity, November 2007, p. 5361-5367, Vol. 75, No. 11
0019-9567/07/$08.00+0     doi:10.1128/IAI.02008-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Kukavica-Ibrulj, I., Hamelin, M.-E., Prince, G. A., Gagnon, C., Bergeron, Y., Bergeron, M. G., Boivin, G. (2009). Infection with Human Metapneumovirus Predisposes Mice to Severe Pneumococcal Pneumonia. J. Virol. 83: 1341-1349 [Abstract] [Full Text]  


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