Long pentraxin PTX3 mediates acute inflammatory responses against pneumococcal infection

Seo Hyun Koh, Seul Gi Shin, Maria Jose Andrade, Ryun hee Go, Seonghee Park, Chang Hoon Woo, Jae Hyang Lim

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Streptococcus pneumoniae is an important human pathogen responsible for more than 2 million deaths annually worldwide. The airway epithelium acts as the first-line of defense against pneumococcal infections by regulating acute inflammation against invading pneumococcus. Despite the intact adaptive immunity, failure in early defense due to loss of pattern recognition receptors (PRRs) and/or acute phase proteins (APPs) results in detrimental damage and death. C-reactive protein (CRP), the first found APP, is a member of the pentraxin family of proteins and an important soluble PRR for pneumococcus. CRP and another short pentraxin, serum amyloid P, are critical for acute defense against pneumococcal infection. However, the role of the long pentraxin PTX3 in regulating pneumococcal infections is unknown. In this study, PTX3 expression was upregulated by pneumococcus in epithelial cells and in lungs of mice. In addition, PTX3 potentiated pneumococcal inflammation; overexpression of PTX3 enhanced pneumococcus-induced cytokine expression, whereas knock-down of PTX3 with siPTX3 inhibited the cytokine expression. Furthermore, PTX3 deficiency indeed ameliorated acute inflammation and protected mice against death following pneumococcal infection. Pneumococcal toxin pneumolysin was responsible for PTX3 expression and upregulated PTX3 expression via JNK MAPK signaling. These data implicate PTX3 as a novel therapeutic target for the control of acute inflammation by pneumococcus.

Original languageEnglish
Pages (from-to)671-676
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume493
Issue number1
DOIs
StatePublished - 4 Nov 2017

Keywords

  • Acute pneumococcal inflammation
  • Community acquired pneumonia
  • Mouse model
  • Pentraxin 3
  • Streptococcus pneumoniae

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