| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Pearlman, Eric Clark, Heather L. Calera, José Antonio Skaar, Eric P. Hohl, Tobias M. Chazin, Walter J. Jhingran, Anupam Vareechon, Chairut Sun, Yan de Jesus Carrion, Steven |
| Description |
Author Affiliation: Clark HL ( Department of Ophthalmology and Visual Science, Case Western Reserve University, Cleveland, OH 44106); Jhingran A ( Infectious Disease Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065); Sun Y ( Department of Ophthalmology and Visual Science, Case Western Reserve University, Cleveland, OH 44106); Vareechon C ( Department of Ophthalmology and Visual Science, Case Western Reserve University, Cleveland, OH 44106); de Jesus Carrion S ( Department of Ophthalmology and Visual Science, Case Western Reserve University, Cleveland, OH 44106); Skaar EP ( Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232); Chazin WJ ( Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232); Calera JA ( Instituto de Biología Funcional y Genómica, Centro Mixto del Consejo Superior de Investigaciones Científicas y Universidad de Salamanca, 37002 Salamanca, Spain.); Hohl TM ( Infectious Disease Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065); Pearlman E ( Department of Ophthalmology and Visual Science, Case Western Reserve University, Cleveland, OH 44106) |
| Abstract |
Calprotectin, a heterodimer of S100A8 and S100A9, is an abundant neutrophil protein that possesses antimicrobial activity primarily because of its ability to chelate zinc and manganese. In the current study, we showed that neutrophils from calprotectin-deficient S100A9(-/-) mice have an impaired ability to inhibit Aspergillus fumigatus hyphal growth in vitro and in infected corneas in a murine model of fungal keratitis; however, the ability to inhibit hyphal growth was restored in S100A9(-/-) mice by injecting recombinant calprotectin. Furthermore, using recombinant calprotectin with mutations in either the Zn and Mn binding sites or the Mn binding site alone, we show that both zinc and manganese binding are necessary for calprotectin's antihyphal activity. In contrast to hyphae, we found no role for neutrophil calprotectin in uptake or killing of intracellular A. fumigatus conidia either in vitro or in a murine model of pulmonary aspergillosis. We also found that an A. fumigatus ∆zafA mutant, which demonstrates deficient zinc transport, exhibits impaired growth in infected corneas and following incubation with neutrophils or calprotectin in vitro as compared with wild-type. Collectively, these studies demonstrate a novel stage-specific susceptibility of A. fumigatus to zinc and manganese chelation by neutrophil-derived calprotectin. |
| ISSN |
00221767 |
| e-ISSN |
15506606 |
| Journal |
The Journal of Immunology |
| Issue Number |
1 |
| Volume Number |
196 |
| Language |
English |
| Publisher |
The American Association of Immunologists |
| Publisher Date |
2016-01-01 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Aspergillus Fumigatus Growth & Development Keratitis Microbiology Leukocyte L1 Antigen Complex Metabolism Manganese Neutrophils Immunology Pulmonary Aspergillosis Zinc Adolescent Animals Biological Transport Genetics Calgranulin A Calgranulin B Chelating Agents Cornea Disease Models, Animal Hyphae Mice Mice, Inbred C57bl Mice, Knockout Phagocytosis Spores, Fungal Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Discipline Immunology |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Immunology and Allergy Immunology |
