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Infect. Immun. doi:10.1128/IAI.00014-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Immune control of the rapid-grower Mycobacterium abscessus in C57BL/6 mice: importance of T cells, interferon and tumor necrosis factor

Laboratoire de Microbiologie, Hôpital R. Poincaré (AP-HP), and EA 3647, Université de Versailles Saint-Quentin, Faculté de Médecine Paris-Ile de France-Ouest, 92380 Garches, Laboratoire d'Anatomo-Pathologie, Hôpital A. Paré (AP-HP), 92100 Boulogne, Unité d'Immunologie et d'Hématologie, Hôpital Necker-Enfants Malades (AP-HP) and Laboratory of Human Genetics of Infectious Diseases, Université René Descartes-INSERM U550, Faculté de Médecine Necker-Enfants Malades, 75730 Paris cedex 15, France, U.E.

^* To whom correspondence should be addressed. Email: martin.rottman{at}rpc.aphp.fr.

	Abstract

Mycobacterium abscessus is an emerging rapidly growing mycobacterium causing tuberculous-like lesions in humans. We studied its immune control in C57BL/6 mice challenged intravenously with 10⁷ CFUs. Bacteria were eliminated from both the spleen and liver within 90 days, with liver histology showing organized granulomatous lesions. T- and B-cell requirement was investigated by challenging Rag2^-/-, Cd3^-/- and µMT^-/- mice. Rag2^-/- and Cd3^-/- mice were significantly impaired in their ability to clear M. abscessus from the liver and spleen, and µMT^-/- mice to clear the liver, suggesting that infection control was primarily T-cell dependent in the spleen and both T- and B-cell dependent in the liver. The liver granulomatous response was similar to wild-type controls in µMT^-/- mice, but completely absent in Cd3^-/- and Rag2^-/- mice. We studied the involvement of interferon (IFN) and tumor necrosis factor (TNF) by challenging C57BL/6 mice deficient in IFN receptor (Ifngr1^-/-) and in TNF (Tnf ^-/-). Ifngr1^-/- mice were significantly impaired in M. abscessus control both in the spleen and liver, with profoundly altered granulomas. The effect was even more substantial in Tnf ^-/- mice: they failed to control M. abscessus infection in the liver and died within 20 to 25 days post-infection with many hepatic inflammatory foci and major lesions of ischemic necrosis in the liver and kidney. These features were not observed with the closely related species, M. chelonae. T-cell immunity, IFN, and TNF are central to the control of M. abscessus in C57BL/6 mice, as they are for pathogenic slow-growing mycobacteria.

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