Evaluation of IL-17D in Host Immunity to Group A Streptococcus Infection.
Allen WashingtonNissi VarkiJ Andrés ValderramaVictor NizetJack D BuiPublished in: Journal of immunology (Baltimore, Md. : 1950) (2020)
IL-17D is a cytokine that belongs to the IL-17 family and is conserved in vertebrates and invertebrates. In contrast to IL-17A and IL-17F, which are expressed in Th17 cells, IL-17D is expressed broadly in nonimmune cells. IL-17D can promote immune responses to cancer and viruses in part by inducing chemokines and recruiting innate immune cells such as NK cells. Although bacterial infection can induce IL-17D in fish and invertebrates, the role of mammalian IL-17D in antibacterial immunity has not been established. To determine whether IL-17D has a role in mediating host defense against bacterial infections, we studied i.p. infection by group A Streptococcus (GAS) in wild-type (WT) and Il17d -/- mice. Compared with WT animals, mice deficient in IL-17D experienced decreased survival, had greater weight loss, and showed increased bacterial burden in the kidney and peritoneal cavity following GAS challenge. In WT animals, IL-17D transcript was induced by GAS infection and correlated to increased levels of chemokine CCL2 and greater neutrophil recruitment. Of note, GAS-mediated IL-17D induction in nonimmune cells required live bacteria, suggesting that processes beyond recognition of pathogen-associated molecular patterns were required for IL-17D induction. Based on our results, we propose a model in which nonimmune cells can discriminate between nonviable and viable GAS cells, responding only to the latter by inducing IL-17D.
Keyphrases
- induced apoptosis
- immune response
- weight loss
- squamous cell carcinoma
- escherichia coli
- type diabetes
- bariatric surgery
- toll like receptor
- cell cycle arrest
- young adults
- cystic fibrosis
- pseudomonas aeruginosa
- adipose tissue
- magnetic resonance imaging
- staphylococcus aureus
- metabolic syndrome
- computed tomography
- inflammatory response
- endoplasmic reticulum stress
- weight gain
- skeletal muscle
- risk factors
- dendritic cells
- single cell
- carbon dioxide
- obese patients
- liver fibrosis