Mice deficient in NKLAM have attenuated inflammatory cytokine production in a Sendai virus pneumonia model

English version

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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Mice deficient in NKLAM have attenuated inflammatory cytokine production in a Sendai virus pneumonia model

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