Regulation of Pulmonary Bacterial Immunity by Follistatin-Like Protein 1.

Autor:	Henkel M; Division of Pediatric Infectious Diseases, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.; UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.; Richard K. Mellon Institute for Pediatric Research, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA., Dutta JA; Division of Pediatric Infectious Diseases, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.; Richard K. Mellon Institute for Pediatric Research, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.; Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Partyka J; Division of Pediatric Infectious Diseases, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.; UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.; Richard K. Mellon Institute for Pediatric Research, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA., Eddens T; Division of Pediatric Infectious Diseases, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.; UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA., Hirsch R; Department of Pediatrics, University of California at San Francisco School of Medicine, San Francisco, California, USA.; Benioff Children's Hospitals, San Francisco, California, USA., Kolls JK; UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.; Richard K. Mellon Institute for Pediatric Research, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA., Campfield BT; Division of Pediatric Infectious Diseases, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA brian.campfield@chp.edu.; UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.; Richard K. Mellon Institute for Pediatric Research, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Jazyk:	angličtina
Zdroj:	Infection and immunity [Infect Immun] 2020 Dec 15; Vol. 89 (1). Date of Electronic Publication: 2020 Dec 15 (Print Publication: 2020).
DOI:	10.1128/IAI.00298-20
Abstrakt:	Klebsiella pneumoniae is a common cause of antibiotic-resistant pneumonia. Follistatin-like protein 1 (FSTL-1) is highly expressed in the lung and is critical for lung homeostasis. The role of FSTL-1 in immunity to bacterial pneumonia is unknown. Wild-type (WT) and FSTL-1 hypomorphic (Hypo) mice were infected with Klebsiella pneumoniae to determine infectious burden, immune cell abundance, and cytokine production. FSTL-1 Hypo/TCRδ -/- and FSTL-1 Hypo/IL17ra -/- were also generated to assess the role of γδT17 cells in this model. FSTL-1 Hypo mice had reduced K. pneumoniae lung burden compared with that of WT controls. FSTL-1 Hypo mice had increased Il17a /interleukin-17A (IL-17A) and IL-17-dependent cytokine expression. FSTL-1 Hypo lungs also had increased IL-17A + and TCRγδ + cells. FSTL-1 Hypo/TCRδ -/- displayed a lung burden similar to that of FSTL-1 Hypo and reduced lung burden compared with the TCRδ -/- controls. However, FSTL-1 Hypo/TCRδ -/- mice had greater bacterial dissemination than FSTL-1 Hypo mice, suggesting that gamma delta T (γδT) cells are dispensable for FSTL-1 Hypo control of pulmonary infection but are required for dissemination control. Confusing these observations, FSTL-1 Hypo/TCRδ -/- lungs had an increased percentage of IL-17A-producing cells compared with that of TCRδ -/- mice. Removal of IL-17A signaling in the FSTL-1 Hypo mouse resulted in an increased lung burden. These findings identify a novel role for FSTL-1 in innate lung immunity to bacterial infection, suggesting that FSTL-1 influences type-17 pulmonary bacterial immunity. (Copyright © 2020 American Society for Microbiology.)
Databáze:	MEDLINE
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