Macrophage-mediated responses to Candida albicans in mice expressing the human immunodeficiency virus type 1 transgene.
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/HIV(MutA) 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 H(2)O(2) 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 H(2)O(2) 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.
Goupil
Mathieu
M
Departments of Microbiology and Immunology, University of Montreal, Montreal, Quebec, Canada.
Trudelle
Emilie Bélanger
EB
Dugas
Véronique
V
Racicot-Bergeron
Catherine
C
Aumont
Francine
F
Sénéchal
Serge
S
Hanna
Zaher
Z
Jolicoeur
Paul
P
de Repentigny
Louis
L
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D002176:Candida albicans / Q000276:immunology*; D002180:Candidiasis, Oral / Q000276:immunology; D016764:Cell Polarity; D005260:Female; D005753:Gastric Mucosa / Q000382:microbiology; D015497:HIV-1 / Q000235:genetics*; D006861:Hydrogen Peroxide / Q000378:metabolism; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008822:Mice, Transgenic; D009061:Mouth Mucosa / Q000382:microbiology; D052247:Nitric Oxide Synthase Type II / Q000502:physiology; D010587:Phagocytosis; D019076:Transgenes; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D014409:Tumor Necrosis Factor-alpha; D006861:Hydrogen Peroxide; D052247:Nitric Oxide Synthase Type II