Subverting host immunity to intracellular pathogens

Scientists have identified a mechanism that allows infections such as Mycobacterium tuberculosis to avoid effective immune responses. The work provides a possible new target for treating diseases caused by many types of pathogens.

Activated immune cells called macrophages are important in combating infections. A key anti-microbial molecule produced by the macrophages is nitric oxide (NO), a noxious gas required for control of infections caused by Mycobacterium tuberculosis, Leishmania cruzi and other infectious agents.

Online in Nature Immunology this week, Peter Murray and colleagues report that such illness causing agents activate the expression of an enzyme in macrophages called arginase 1 that reduces the amount of NO activity in the macrophages. By inducing arginase 1, these agents avoid a natural and otherwise effective response to infection. When arginase 1 is eliminated from macrophages, for example, lung bacterial load during tuberculosis infection is significantly reduced.

By pinpointing how these intracellular pathogens evade the immune system, the study highlights a unique 'loophole' in the normal immune response to these infectious agents.

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 M 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

Published online: 02 November 2008 | doi 10.1038/ni.1671

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