Damping excessive inflammation and tissue damage in Mycobacterium tuberculosis infection by toll IL-1 receptor 8/single Ig IL-1-related receptor, a negative regulator of IL-1/TLR signaling

Cecilia Garlanda, Diana Di Liberto, Annunciata Vecchi, Marco P. La Manna, Chiara Buracchi, Nadia Caccamo, Alfredo Salerno, Francesco Dieli, Alberto Mantovani

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Abstract

Toll IL-1R 8/single Ig IL-1-related receptor (TIR8/SIGIRR) is a member of the IL-1R family, expressed by epithelial tissues and immature dendritic cells, and is regarded as a negative regulator of TLR/IL-1R signaling. Tir8-deficient mice were rapidly killed by intranasal administration of low doses of Mycobacterium tuberculosis, despite controlling efficiently the number of viable bacilli in different organs. Tir8-/--infected mice showed an increased number of neutrophils and macrophages in the lungs; however, mycobacteria-specific CD4 and CD8 T cells were similar in Tir8-/- and Tir8+/+ mice. Exaggerated mortality of Tir8-/- mice was due to massive liver necrosis and was accompanied by increased levels of IL-1β and TNF-α in lung mononuclear cells and serum, as well as by increased production of IL-1β and TNF-α by M. tuberculosis-infected dendritic cells in vitro. Accordingly, blocking IL-1α and TNF-β with a mix of anti-cytokine Abs, significantly prolonged survival of Tir8 -/- mice. Thus, TIR8/SIGIRR plays a key role in damping inflammation and tissue damage in M. tuberculosis infection.

Original languageEnglish
Pages (from-to)3119-3125
Number of pages7
JournalJournal of Immunology
Volume179
Issue number5
Publication statusPublished - Sep 1 2007

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Mycobacterium Infections
Interleukin-1 Receptors
Interleukin-1
Mycobacterium tuberculosis
Inflammation
Interleukin-8
Dendritic Cells
Intranasal Administration
Lung
Mycobacterium
Bacillus
Neutrophils
Necrosis
Epithelium
Macrophages
Cytokines
T-Lymphocytes
Mortality
Liver
Serum

ASJC Scopus subject areas

  • Immunology

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Damping excessive inflammation and tissue damage in Mycobacterium tuberculosis infection by toll IL-1 receptor 8/single Ig IL-1-related receptor, a negative regulator of IL-1/TLR signaling. / Garlanda, Cecilia; Di Liberto, Diana; Vecchi, Annunciata; La Manna, Marco P.; Buracchi, Chiara; Caccamo, Nadia; Salerno, Alfredo; Dieli, Francesco; Mantovani, Alberto.

In: Journal of Immunology, Vol. 179, No. 5, 01.09.2007, p. 3119-3125.

Research output: Contribution to journalArticle

Garlanda, Cecilia ; Di Liberto, Diana ; Vecchi, Annunciata ; La Manna, Marco P. ; Buracchi, Chiara ; Caccamo, Nadia ; Salerno, Alfredo ; Dieli, Francesco ; Mantovani, Alberto. / Damping excessive inflammation and tissue damage in Mycobacterium tuberculosis infection by toll IL-1 receptor 8/single Ig IL-1-related receptor, a negative regulator of IL-1/TLR signaling. In: Journal of Immunology. 2007 ; Vol. 179, No. 5. pp. 3119-3125.
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