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

Abstract:

: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.

journal_name

Infect Immun

journal_title

Infection and immunity

authors

Lindell DM,Standiford TJ,Mancuso P,Leshen ZJ,Huffnagle GB

doi

10.1128/IAI.69.10.6364-6369.2001

keywords:

subject

Has Abstract

pub_date

2001-10-01 00:00:00

pages

6364-9

issue

10

eissn

0019-9567

issn

1098-5522

journal_volume

69

pub_type

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