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Infection and Immunity, October 2001, p. 6364-6369, Vol. 69, No. 10
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.10.6364-6369.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Macrophage Inflammatory Protein 1alpha /CCL3 Is Required for Clearance of an Acute Klebsiella pneumoniae Pulmonary Infection

Dennis M. Lindell,1 Theodore J. Standiford,1 Peter Mancuso,2 Zachary J. Leshen,1 and Gary B. Huffnagle1,*

Pulmonary and Critical Care Medicine, The University of Michigan Medical School,1 and Environmental Health Sciences, University of Michigan School of Public Health,2 Ann Arbor, Michigan

Received 25 April 2001/Returned for modification 14 June 2001/Accepted 10 July 2001

The objective of these studies was to determine the role of macrophage inflammatory protein 1alpha /CCL3 in pulmonary host defense during Klebsiella pneumoniae infection. Following intratracheal inoculation, 7-day survival of CCL3-/- mice was less than 10%, compared to 60% for CCL3+/+ mice. Survival of CCR5-/- mice was equivalent to that of controls, indicating that the enhanced susceptibility of CCL3-/- mice to K. pneumoniae is mediated via another CCL3 receptor, presumably CCR1. At day 3, CFU burden in the lungs of CCL3-/- mice was 800-fold higher than in CCL3+/+ mice, demonstrating that CCL3 is critical for control of bacterial growth in the lung. Surprisingly, CCL3-/- mice had no differences in the recruitment of monocytes/macrophages and even showed enhanced neutrophil recruitment at days 1, 2, and 3 postinfection, compared to CCL3+/+ mice. Therefore, the defect in clearance was not due to insufficient recruitment of leukocytes. No significant differences in cytokine levels of monocyte chemoattractant protein 1 (MCP-1), interleukin 12, gamma interferon, or tumor necrosis factor alpha in lung lavages were found between CCL3+/+ and CCL3-/- mice. CCL3-/- alveolar macrophages were found to have significantly lower phagocytic activity toward K. pneumoniae than CCL3+/+ alveolar macrophages. These findings demonstrate that CCL3 production is critical for activation of alveolar macrophages to control the pulmonary growth of the gram-negative bacterium K. pneumoniae.

* Corresponding author. Mailing address: Pulmonary and Critical Care Medicine, 6301 MSRB III, University of Michigan Medical Center, Ann Arbor, MI 48109-0642. Phone: (734) 936-9369. Fax: (734) 764-4556. E-mail: ghuff{at}umich.edu.

Infection and Immunity, October 2001, p. 6364-6369, Vol. 69, No. 10
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.10.6364-6369.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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