Endothelial nitric oxide synthase limits host immunity to control disseminated Candida albicans infections in mice

Autor: Dhammika H. M. L. P. Navarathna, David D. Roberts, Michail S. Lionakis
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Chemokine
Physiology
Nitric Oxide Synthase Type II
Yeast and Fungal Models
Pathology and Laboratory Medicine
Kidney
Biochemistry
Mice
0302 clinical medicine
Spectrum Analysis Techniques
Enos
Immune Physiology
Candida albicans
Medicine and Health Sciences
Immune Response
Candida
Fungal Pathogens
Innate Immune System
Multidisciplinary
biology
Candidiasis
Eukaryota
Neurochemistry
Flow Cytometry
3. Good health
Up-Regulation
Nitric oxide synthase
Infectious Diseases
Experimental Organism Systems
Neutrophil Infiltration
Medical Microbiology
Spectrophotometry
Medicine
Cytokines
Cytophotometry
medicine.symptom
Anatomy
Pathogens
Neurochemicals
Research Article
Nitric Oxide Synthase Type III
Science
Urology
Immunology
Sexually Transmitted Diseases
Inflammation
Mycology
Research and Analysis Methods
Nitric Oxide
Microbiology
03 medical and health sciences
Immune system
Signs and Symptoms
Diagnostic Medicine
medicine
Animals
Microbial Pathogens
Innate immune system
Genitourinary Infections
Organisms
Fungi
Biology and Life Sciences
Kidneys
Renal System
Molecular Development
biology.organism_classification
Yeast
Mice
Inbred C57BL
030104 developmental biology
Immune System
biology.protein
Animal Studies
Leukocyte chemotaxis
Gene Deletion
030215 immunology
Developmental Biology
Neuroscience
Zdroj: PLoS ONE
PLoS ONE, Vol 14, Iss 10, p e0223919 (2019)
ISSN: 1932-6203
Popis: Three isoforms of nitric oxide synthase (NOS) occur in mammals. High levels of NO produced by NOS2/iNOS can protect against bacterial and parasitic infections, but the role of NOS in fungal innate immunity is less clear. Compared to wild type mice, Nos3-/- mice showed significantly higher survival of candidemia caused by Candida albicans SC5314. NOS3/eNOS is expressed by endothelial cells in the kidney, and colonization of this organ was decreased during the sub-acute stage of disseminated candidiasis. Nos3-/- mice more rapidly eliminated Candida from the renal cortex and exhibited more balanced local inflammatory reactions, with similar macrophage but less neutrophil infiltration than in infected wild type. Levels of the serum cytokines IL-9, IL-12, IL-17 and chemokines GM-CSF, MIP1α, and MIP1β were significantly elevated, and IL-15 was significantly lower in infected Nos3-/- mice. Spleens of infected Nos3-/- mice had significantly more Th2 and Th9 but not other CD4+ T cells compared with wild type. Inflammatory genes associated with leukocyte chemotaxis, IL-1 signaling, TLR signaling and Th1 and Th2 cell differentiation pathways were significantly overexpressed in infected Nos3-/- kidneys, with Nos2 being the most strongly induced. Conversely, the general NOS inhibitor NG-nitro-L-arginine methyl ester increased virulence in the mouse candidemia model, suggesting that iNOS contributes to the protective mechanism in infected Nos3-/- mice. By moderating neutrophil infiltration, the absence of eNOS may reduce the collateral damage to kidney cortex, and Th-9 CD4+ cells may enhance clearance of the infection. These data suggest that selective eNOS inhibition could mitigate candidemia by a combination of systemic and local responses that promote a more effective host immune response.
Databáze: OpenAIRE
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