Toll-like receptor-induced arginase 1 in macrophages thwarts effective immunity against intracellular pathogens

Karim C. El Kasmi, Joseph E. Qualls, John T. Pesce, Amber Smith, Robert W. Thompson, Marcela Henao-Tamayo, Randall J. Basaraba, Till König, Ulrike Schleicher, Mi Sun Koo, Gilla Kaplan, Katherine A. Fitzgerald, Elaine I. Tuomanen, Ian M. Orme, Thirumala Devi Kanneganti, Christian Bogdan, Thomas A. Wynn, Peter J. Murray

Research output: Contribution to journalArticle

356 Citations (Scopus)

Abstract

Toll-like receptor (TLR) signaling in macrophages is required for antipathogen responses, including the biosynthesis of nitric oxide from arginine, and is essential for immunity to Mycobacterium tuberculosis, Toxoplasma gondii and other intracellular pathogens. Here we report a 'loophole' in the TLR pathway that is advantageous to these pathogens. Intracellular pathogens induced expression of the arginine hydrolytic enzyme arginase 1 (Arg1) in mouse macrophages through the TLR pathway. In contrast to diseases dominated by T helper type 2 responses in which Arg1 expression is greatly increased by interleukin 4 and 13 signaling through the transcription factor STAT6, TLR-mediated Arg1 induction was independent of the STAT6 pathway. Specific elimination of Arg1 in macrophages favored host survival during T. gondii infection and decreased lung bacterial load during tuberculosis infection.

Original languageEnglish (US)
Pages (from-to)1399-1406
Number of pages8
JournalNature Immunology
Volume9
Issue number12
DOIs
StatePublished - Oct 31 2008

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Arginase
Toll-Like Receptors
Immunity
Macrophages
Arginine
STAT6 Transcription Factor
Interleukin-13
Bacterial Load
Toxoplasmosis
Toxoplasma
Mycobacterium tuberculosis
Interleukin-4
Nitric Oxide
Tuberculosis
Lung
Enzymes
Infection

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

El Kasmi, K. C., Qualls, J. E., Pesce, J. T., Smith, A., Thompson, R. W., Henao-Tamayo, M., ... Murray, P. J. (2008). Toll-like receptor-induced arginase 1 in macrophages thwarts effective immunity against intracellular pathogens. Nature Immunology, 9(12), 1399-1406. https://doi.org/10.1038/ni.1671

Toll-like receptor-induced arginase 1 in macrophages thwarts effective immunity against intracellular pathogens. / El Kasmi, Karim C.; Qualls, Joseph E.; Pesce, John T.; Smith, Amber; Thompson, Robert W.; Henao-Tamayo, Marcela; Basaraba, Randall J.; König, Till; Schleicher, Ulrike; Koo, Mi Sun; Kaplan, Gilla; Fitzgerald, Katherine A.; Tuomanen, Elaine I.; Orme, Ian M.; Kanneganti, Thirumala Devi; Bogdan, Christian; Wynn, Thomas A.; Murray, Peter J.

In: Nature Immunology, Vol. 9, No. 12, 31.10.2008, p. 1399-1406.

Research output: Contribution to journalArticle

El Kasmi, KC, Qualls, JE, Pesce, JT, Smith, A, Thompson, RW, Henao-Tamayo, M, Basaraba, RJ, König, T, Schleicher, U, Koo, MS, Kaplan, G, Fitzgerald, KA, Tuomanen, EI, Orme, IM, Kanneganti, TD, Bogdan, C, Wynn, TA & Murray, PJ 2008, 'Toll-like receptor-induced arginase 1 in macrophages thwarts effective immunity against intracellular pathogens', Nature Immunology, vol. 9, no. 12, pp. 1399-1406. https://doi.org/10.1038/ni.1671
El Kasmi, Karim C. ; Qualls, Joseph E. ; Pesce, John T. ; Smith, Amber ; Thompson, Robert W. ; Henao-Tamayo, Marcela ; Basaraba, Randall J. ; König, Till ; Schleicher, Ulrike ; Koo, Mi Sun ; Kaplan, Gilla ; Fitzgerald, Katherine A. ; Tuomanen, Elaine I. ; Orme, Ian M. ; Kanneganti, Thirumala Devi ; Bogdan, Christian ; Wynn, Thomas A. ; Murray, Peter J. / Toll-like receptor-induced arginase 1 in macrophages thwarts effective immunity against intracellular pathogens. In: Nature Immunology. 2008 ; Vol. 9, No. 12. pp. 1399-1406.
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