Journal article
Glutathione Reductase Promotes Fungal Clearance and Suppresses Inflammation during Systemic Candida albicans Infection in Mice
The Journal of immunology (1950), Vol.203(8), pp.2239-2251
10/15/2019
DOI: 10.4049/jimmunol.1701686
PMCID: PMC6783371
PMID: 31501257
Abstract
Glutathione reductase (Gsr) catalyzes the reduction of glutathione disulfide to glutathione, which plays an important role in redox regulation. We have previously shown that Gsr facilitates neutrophil bactericidal activities and is pivotal for host defense against bacterial pathogens. However, it is unclear whether Gsr is required for immune defense against fungal pathogens. It is also unclear whether Gsr plays a role in immunological functions outside of neutrophils during immune defense. In this study, we report that
mice exhibited markedly increased susceptibility to
challenge. Upon
infection,
mice exhibited dramatically increased fungal burden in the kidneys, cytokine and chemokine storm, striking neutrophil infiltration, histological abnormalities in both the kidneys and heart, and substantially elevated mortality. Large fungal foci surrounded by massive numbers of neutrophils were detected outside of the glomeruli in the kidneys of
mice but were not found in wild-type mice. Examination of the neutrophils and macrophages of
mice revealed several defects.
neutrophils exhibited compromised phagocytosis, attenuated respiratory burst, and impaired fungicidal activity in vitro. Moreover, upon
stimulation,
macrophages produced increased levels of inflammatory cytokines and exhibited elevated p38 and JNK activities, at least in part, because of lower MAPK phosphatase (Mkp)-1 activity and greater Syk activity. Thus, Gsr-mediated redox regulation is crucial for fungal clearance by neutrophils and the proper control of the inflammatory response by macrophages during host defense against fungal challenge.
Details
- Title: Subtitle
- Glutathione Reductase Promotes Fungal Clearance and Suppresses Inflammation during Systemic Candida albicans Infection in Mice
- Creators
- Victoria Y Kim - Nationwide Children's HospitalAbel Batty - Nationwide Children's HospitalJinhui Li - Nationwide Children's HospitalSean G Kirk - Nationwide Children's HospitalSara A Crowell - Nationwide Children's HospitalYi Jin - Nationwide Children's HospitalJuan Tang - Central South UniversityJian Zhang - University of Iowa, PathologyLynette K Rogers - University of Iowa, Holden Comprehensive Cancer CenterHan-Xiang Deng - Northwestern UniversityLeif D Nelin - Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH 43205; andYusen Liu - Nationwide Children's Hospital
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.203(8), pp.2239-2251
- DOI
- 10.4049/jimmunol.1701686
- PMID
- 31501257
- PMCID
- PMC6783371
- NLM abbreviation
- J Immunol
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Grant note
- R01 AI121196 / NIAID NIH HHS R01 AI124029 / NIAID NIH HHS R21 AI113930 / NIAID NIH HHS R01 AI123253 / NIAID NIH HHS R01 AI090901 / NIAID NIH HHS R21 AI142885 / NIAID NIH HHS
- Language
- English
- Date published
- 10/15/2019
- Academic Unit
- Pathology
- Record Identifier
- 9984195952602771
Metrics
18 Record Views