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Infection and Immunity, September 2009, p. 4136-4149, Vol. 77, No. 9
0019-9567/09/$08.00+0 doi:10.1128/IAI.00453-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Macrophage-Mediated Responses to Candida albicans in Mice Expressing the Human Immunodeficiency Virus Type 1 Transgene 
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Mathieu Goupil,1,
Émilie Bélanger Trudelle,1,
Véronique Dugas,1
Catherine Racicot-Bergeron,1
Francine Aumont,1
Serge Sénéchal,1
Zaher Hanna,2,4,5
Paul Jolicoeur,1,4,5 and
Louis de Repentigny1,3*
Departments of Microbiology and Immunology,1 Medicine, Faculty of Medicine, University of Montreal,2 Sainte-Justine Hospital,3 Laboratory of Molecular Biology, Clinical Research Institute of Montreal,4 Division of Experimental Medicine, McGill University, Montreal, Quebec, Canada5
Received 22 April 2009/ Returned for modification 27 May 2009/ Accepted 20 June 2009
The critical impairments of innate and adaptive immunity that cause susceptibility to mucosal candidiasis in human immunodeficiency virus (HIV) infection have not been fully determined. We therefore conducted an analysis of macrophage-mediated responses to Candida albicans in transgenic (Tg) mice expressing Nef, Env, and Rev of HIV type 1 (HIV-1) in CD4+ T cells, dendritic cells, and macrophages and developing an AIDS-like disease (CD4C/HIVMutA Tg mice). Macrophages were successfully recruited to the oral and gastric mucosae of these Tg mice in response to chronic carriage of C. albicans and displayed polarization toward an alternatively activated phenotype. Functionally, peritoneal macrophages from uninfected Tg mice exhibited increased phagocytosis of C. albicans and enhanced production of interleukin 6 and monocyte chemoattractant protein 1, demonstrating that the HIV-1 transgene independently activates selected macrophage functions. Production of H2O2 by macrophages from Tg mice primed with gamma interferon and treated with phorbol 12-myristate 13-acetate or C. albicans was moderately reduced, but expression of the HIV-1 transgene did not alter production of nitric oxide or reduce killing of C. albicans. A knockout of the inducible nitric oxide synthase (NOS2) gene in these Tg mice did not augment oral or gastrointestinal burdens during chronic carriage of C. albicans or cause systemic dissemination, likely due to a redundancy provided by partially preserved production of H2O2 and oxygen-independent candidacidal mechanisms. Thus, the macrophage response to C. albicans is largely preserved in these Tg mice, and no functional macrophage defect appears to primarily determine the susceptibility to mucosal candidiasis.
* Corresponding author. Mailing address: Department of Microbiology and Immunology, Sainte-Justine Hospital and University of Montreal, 3175 Côte Ste-Catherine, Montreal, QC, H3T 1C5, Canada. Phone: (514) 345-4643. Fax: (514) 345-4860. E-mail: louis.de.repentigny{at}umontreal.ca
Published ahead of print on 29 June 2009.
Supplemental material for this article may be found at http://iai.asm.org/.
These authors contributed equally to this work.
Infection and Immunity, September 2009, p. 4136-4149, Vol. 77, No. 9
0019-9567/09/$08.00+0 doi:10.1128/IAI.00453-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
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