CX3CR1-dependent renal macrophage survival promotes Candida control and host survival
| Autor: | Philip M. Murphy, Theo S. Plantinga, Jean K. Lim, Martin Jaeger, Muthulekha Swamydas, Ji Liang Gao, John C. Yang, Constantinos M. Mikelis, Barbara D. Alexander, John R. Perfect, Chyi-Chia Richard Lee, Andrius Masedunskas, Brett G. Fischer, Wuzhou Wan, Nathaniel M. Green, Greg M. Laird, Bart Jan Kullberg, Melissa D. Johnson, Robert T. Wheeler, Michail S. Lionakis, Roberto Weigert, Aymeric Rivollier, Mihai G. Netea |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Adoptive cell transfer Apoptosis Kidney Monocytes Pathogenesis Chemokine receptor Mice 0302 clinical medicine Cell Movement Risk Factors CX3CR1 Candida albicans Chemokine CCL2 Netherlands 0303 health sciences biology General Medicine Adoptive Transfer 3. Good health Specific Pathogen-Free Organisms Pathogenesis and modulation of inflammation [N4i 1] medicine.anatomical_structure Organ Specificity Radiation Chimera Host-Pathogen Interactions Models Animal Female Receptors Chemokine Receptors CCR2 CX3C Chemokine Receptor 1 Hyphae Invasive mycoses and compromised host Infection and autoimmunity [N4i 2] Polymorphism Single Nucleotide Invasive mycoses and compromised host [N4i 2] 03 medical and health sciences medicine Animals Humans Candidiasis Invasive Genetic Predisposition to Disease 030304 developmental biology Adaptor Proteins Signal Transducing Innate immune system Chemokine CX3CL1 Macrophages Pathogenesis and modulation of inflammation Infection and autoimmunity [N4i 1] Macrophage Activation medicine.disease biology.organism_classification United States Mice Inbred C57BL Immunology Systemic candidiasis 030215 immunology |
| Zdroj: | Journal of Clinical Investigation, 123, 5035-51 Journal of Clinical Investigation, 123, 12, pp. 5035-51 |
| ISSN: | 0021-9738 |
| Popis: | Contains fulltext : 125417.pdf (Publisher’s version ) (Open Access) Systemic Candida albicans infection causes high morbidity and mortality and is associated with neutropenia; however, the roles of other innate immune cells in pathogenesis are poorly defined. Here, using a mouse model of systemic candidiasis, we found that resident macrophages accumulated in the kidney, the main target organ of infection, and formed direct contacts with the fungus in vivo mainly within the first few hours after infection. Macrophage accumulation and contact with Candida were both markedly reduced in mice lacking chemokine receptor CX3CR1, which was found almost exclusively on resident macrophages in uninfected kidneys. Infected Cx3cr1-/- mice uniformly succumbed to Candida-induced renal failure, but exhibited clearance of the fungus in all other organs tested. Renal macrophage deficiency in infected Cx3cr1-/- mice was due to reduced macrophage survival, not impaired proliferation, trafficking, or differentiation. In humans, the dysfunctional CX3CR1 allele CX3CR1-M280 was associated with increased risk of systemic candidiasis. Together, these data indicate that CX3CR1-mediated renal resident macrophage survival is a critical innate mechanism of early fungal control that influences host survival in systemic candidiasis. |
| Databáze: | OpenAIRE |
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