Interleukin-1 signaling is essential for host defense during murine pulmonary tuberculosis.
Interleukin (IL)-1 signaling is required for the containment of infections with intracellular microorganisms, such as Listeria monocytogenes and Leishmania major. To determine the role of IL-1 in the host response to tuberculosis, we infected IL-1 type I receptor-deficient (IL-1R(-/-)) mice, in which IL-1 does not exert effects, with Mycobacterium tuberculosis. IL-1R(-/-) mice were more susceptible to pulmonary tuberculosis, as reflected by an increased mortality and an enhanced mycobacterial outgrowth in lungs and distant organs, which was associated with defective granuloma formation, containing fewer macrophages and fewer lymphocytes, whereas granulocytes were abundant. Lymphocytes were predominantly confined to perivascular areas, suggesting a defective migration of cells into inflamed tissue in the absence of IL-1 signaling. Impaired host defense in IL-1R(-/-) mice was further characterized by a decrease in the ability of splenocytes to produce interferon-gamma. Analysis of these data suggests that IL-1 plays an important role in the immune response to M. tuberculosis.
Juffermans
N P
NP
Laboratory of Experimental Internal Medicine, Department of Internal Medicine, Division of Infectious Diseases, Tropical Medicine, and AIDS, Academic Medical Centre, University of Amsterdam, The Netherlands.
Florquin
S
S
Camoglio
L
L
Verbon
A
A
Kolk
A H
AH
Speelman
P
P
van Deventer
S J
SJ
van Der Poll
T
T
D000818:Animals; D005260:Female; D007375:Interleukin-1 / Q000502:physiology*; D008168:Lung / Q000473:pathology; D016131:Lymphocyte Subsets / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017472:Receptors, Interleukin-1 / Q000502:physiology; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology; D018417:Th1 Cells / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000276:immunology*
D007375:Interleukin-1; D017472:Receptors, Interleukin-1