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Infection and Immunity, January 2009, p. 196-204, Vol. 77, No. 1
0019-9567/09/$08.00+0     doi:10.1128/IAI.01011-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

A Hemidominant Naip5 Allele in Mouse Strain MOLF/Ei-Derived Macrophages Restricts Legionella pneumophila Intracellular Growth {triangledown}

Vicki P. Losick,2,{dagger} Kristin Stephan,3,{dagger} Irina I. Smirnova,3 Ralph R. Isberg,1,2 and Alexander Poltorak3*

Howard Hughes Medical Institute,1 Departments of Molecular Biology and Microbiology,2 Pathology, Tufts University School of Medicine, 150 Harrison Ave., Boston, Massachusetts 021113

Received 12 August 2008/ Returned for modification 19 September 2008/ Accepted 29 October 2008

Mouse-derived macrophages have the unique ability to restrict or permit Legionella pneumophila intracellular growth. The common inbred mouse strain C57BL/6J (B6) restricts L. pneumophila growth, whereas macrophages derived from A/J mice allow >103-fold bacterial growth within three days. This phenotypic difference was mapped to the mouse Naip5 allele. The B6 restrictive Naip5 allele is dominant, and six amino acid changes in its product were predicted to control permissiveness. By using the wild-derived mouse strain MOLF/Ei, we found that MOLF/Ei-derived macrophages also restrict L. pneumophila growth, yet the Naip5 protein is identical to the A/J Naip5 at the six-amino-acid signature. The MOLF/Ei restrictive trait, unlike that of B6-derived macrophages, was not dominant over the A/J trait. In spite of this phenotypic difference, the L. pneumophila growth restriction in MOLF/Ei macrophages was mapped to the Naip5 region as well, indicating that the originally predicted change in the A/J Naip5 allele may not be critical for restriction. In the product of the A/J Naip5 permissive allele, there are four unique amino acid changes that map to a NACHT-like domain. Similar misregulating mutations have been identified in the NACHT domains of Nod-like receptor (NLR) proteins. Therefore, one of these mutations may be critical for restriction of L. pneumophila intracellular growth, and this parallels results found with human NLR variants with defects in the innate immune response.

* Corresponding author. Mailing address: Department of Pathology, Tufts University School of Medicine, 150 Harrison Ave., Boston, MA 02111. Phone: (617) 636-3596. Fax: (617) 636-2990. E-mail: alexander.poltorak{at}tufts.edu

{triangledown} Published ahead of print on 3 November 2008.

Editor: A. J. Bäumler

{dagger} These authors contributed equally to this work.

Infection and Immunity, January 2009, p. 196-204, Vol. 77, No. 1
0019-9567/09/$08.00+0     doi:10.1128/IAI.01011-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Plumlee, C. R., Lee, C., Beg, A. A., Decker, T., Shuman, H. A., Schindler, C. (2009). Interferons Direct an Effective Innate Response to Legionella pneumophila Infection. J. Biol. Chem. 284: 30058-30066 [Abstract] [Full Text]  


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