PloS one, 2019-09, Vol.14 (9), p.e0222802-e0222802
2019
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- Autor(en) / Beteiligte
- Titel
- Mice deficient in NKLAM have attenuated inflammatory cytokine production in a Sendai virus pneumonia model
- Ist Teil von
- PloS one, 2019-09, Vol.14 (9), p.e0222802-e0222802
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2019
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Recent studies have begun to elucidate a role for E3 ubiquitin ligases as important mediators of the innate immune response. Our previous work defined a role for the ubiquitin ligase natural killer lytic-associated molecule (NKLAM/RNF19b) in mouse and human innate immunity. Here, we present novel data describing a role for NKLAM in regulating the immune response to Sendai virus (SeV), a murine model of paramyxoviral pneumonia. NKLAM expression was significantly upregulated by SeV infection. SeV-infected mice that are deficient in NKLAM demonstrated significantly less weight loss than wild type mice. In vivo, Sendai virus replication was attenuated in NKLAM-/- mice. Autophagic flux and the expression of autophagy markers LC3 and p62/SQSTM1 were also less in NKLAM-/- mice. Using flow cytometry, we observed less neutrophils and macrophages in the lungs of NKLAM-/- mice during SeV infection. Additionally, phosphorylation of STAT1 and NFκB p65 was lower in NKLAM-/- than wild type mice. The dysregulated phosphorylation profile of STAT1 and NFκB in NKLAM-/- mice correlated with decreased expression of numerous proinflammatory cytokines that are regulated by STAT1 and/or NFκB. The lack of NKLAM and the resulting attenuated immune response is favorable to NKLAM-/- mice receiving a low dose of SeV; however, at a high dose of virus, NKLAM-/- mice succumbed to the infection faster than wild type mice. In conclusion, our novel results indicate that NKLAM plays a role in regulating the production of pro-inflammatory cytokines during viral infection.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0222802Titel-ID: cdi_plos_journals_2294471233
- Format
- –
- Schlagworte
- Animal models, Animals, Attenuation, Autophagy, Biology and Life Sciences, Care and treatment, Chemokines, Cytokines, Cytokines - genetics, Cytokines - metabolism, Disease Models, Animal, Flow cytometry, Gene expression, Humans, Immune response, Immune system, Immunity, Innate - genetics, Immunology, Infection, Infections, Inflammation, Inflammation Mediators - metabolism, Innate immunity, Laboratory animals, Leukocytes (neutrophilic), Ligases, Macrophages, Macrophages - metabolism, Macrophages - virology, Medicine, Medicine and Health Sciences, Membrane Proteins - deficiency, Membrane Proteins - genetics, Mice, Mice, 129 Strain, Mice, Inbred C57BL, Mice, Knockout, Neutrophils, NF-κB protein, Novels, Pathology, Phagocytosis, Phosphorylation, Pneumonia, Pneumonia - genetics, Pneumonia - metabolism, Pneumonia - virology, Proteins, Research and Analysis Methods, Respirovirus Infections - genetics, Respirovirus Infections - metabolism, Respirovirus Infections - virology, Risk factors, Sendai virus - physiology, Sequestosome-1 Protein - genetics, Sequestosome-1 Protein - metabolism, Signal transduction, Stat1 protein, Stem cells, Streptococcus infections, Transcription Factor RelA - genetics, Transcription Factor RelA - metabolism, Ubiquitin, Ubiquitin-protein ligase, Viral infections, Virus replication, Viruses, Weight loss