Macrophage inflammatory protein 1 alpha CCL3 is required for clearance of an acute Klebsiella pneumoniae pulmonary infection

The objective of these studies was to determine the role of macrophage infl ammatory protein 1 alpha /CCL3 in pulmonary host defense during Klebsiella pneumoniae infection. Following intratracheal inoculation, 7-day survival o f CCL3(-/-) mice was less than 10%, compared to 60% for CCL3(+/+) mice. Sur vival 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 lun gs of CCL3(-/-) mice was 800-fold higher than in CCL3(+/+) mice, demonstrat ing that CCL3 is critical for control of bacterial growth in the lung. Surp risingly, 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 i n clearance was not due to insufficient recruitment of leukocytes. No signi ficant 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 acti vity toward K pneumoniae than CCL3(+/+) alveolar macrophages. These finding s demonstrate that CCL3 production is critical for activation of alveolar m acrophages to control the pulmonary growth of the gram-negative bacterium K . pneumoniae.