Mice deficient in NKLAM have attenuated inflammatory cytokine production in a Sendai virus pneumonia model
Autoři:
Donald W. Lawrence aff001; Laurie P. Shornick aff002; Jacki Kornbluth aff001
Působiště autorů:
Department of Pathology, Saint Louis University School of Medicine, Saint Louis, Missouri, United States of America
aff001; Department of Biology, Saint Louis University, Saint Louis, Missouri, United States of America
aff002; Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, Saint Louis, Missouri, United States of America
aff003; Veterans Affairs Saint Louis Health Care System, Saint Louis, Missouri, United States of America
aff004
Vyšlo v časopise:
PLoS ONE 14(9)
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pone.0222802
Souhrn
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.
Klíčová slova:
Biology and life sciences – Physiology – Physiological parameters – Developmental biology – Molecular development – Biochemistry – Proteins – Post-translational modification – Phosphorylation – Cell biology – Cellular types – Animal cells – Blood cells – White blood cells – Immune cells – Medicine and health sciences – Immune physiology – Body weight – Immunology – Immune system – Innate immune system – Cytokines – Immune response – Inflammation – Diagnostic medicine – Signs and symptoms – Pathology and laboratory medicine – Pulmonology – Respiratory infections – Research and analysis methods – Animal studies – Experimental organism systems – Model organisms – Mouse models – Animal models
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