Mycobacterial lipoarabinomannan induces an inflammatory response in the mouse lung. A role for interleukin-1.
Lipoarabinomannan (LAM), a cell wall component of Mycobacterium tuberculosis, induces the production of cytokines and chemokines in vitro. Interleukin-1 (IL-1) contributes to granuloma formation in tuberculosis (TB), and exerts effects via the IL-1 receptor type I (IL-1R). To determine the effects of LAM in the pulmonary compartment in vivo and to establish the role of endogenous IL-1 herein, normal and IL-1R deficient ((-/-)) mice were intranasally inoculated with LAM (50 microgram). In normal mice, LAM resulted in a neutrophilic cell influx into the bronchoalveolar lavage fluid (BALF). LAM also induced increases in the lung concentrations of macrophage inflammatory protein-2 (MIP-2), keratinocyte (KC), tumor necrosis factor-alpha (TNF-alpha), IL-1alpha, and IL-1beta. IL-1R(-/-) mice had less influx of granulocytes in their BALF than wild-type mice. Also, lung TNF-alpha levels were lower in IL-1R(-/-) mice. LAM may be an important stimulator of innate immunity in infection with M. tuberculosis via mechanisms that involve endogenous IL-1 activity.
Laboratory of Experimental Internal Medicine, Department of Internal Medicine, Division of Infectious Diseases, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. N.Juffermans@amc.uva.nl
N P
NP
Juffermans
A
A
Verbon
J T
JT
Belisle
P J
PJ
Hill
P
P
Speelman
S J
SJ
van Deventer
T
T
van der Poll
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D018925:Chemokines / Q000032:analysis; D007249:Inflammation / Q000209:etiology / Q000276:immunology; D007375:Interleukin-1 / Q000172:deficiency / Q000502:physiology*; D008070:Lipopolysaccharides / Q000276:immunology*; D008168:Lung / Q000276:immunology*; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000942:Antigens, Bacterial; D018925:Chemokines; D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C050016:lipoarabinomannan