Galectin-3 Enhances Avian H5N1 Influenza A Virus–Induced Pulmonary Inflammation by Promoting NLRP3 Inflammasome Activation

Yu Jung Chen, Sheng Fan Wang, I. Chun Weng, Ming Hsiang Hong, Tzu Han Lo, Jia Tsrong Jan, Li Chung Hsu, Huan Yuan Chen, Fu-Tong Liu

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Highly pathogenic avian influenza A H5N1 virus causes pneumonia and acute respiratory distress syndrome in humans. Virus-induced excessive inflammatory response contributes to severe disease and high mortality rates. Galectin-3, a β-galactoside-binding protein widely distributed in immune and epithelial cells, regulates various immune functions and modulates microbial infections. Here, we describe galectin-3 up-regulation in mouse lung tissue after challenges with the H5N1 influenza virus. We investigated the effects of endogenous galectin-3 on H5N1 infection and found that survival of galectin-3 knockout (Gal-3KO) mice was comparable with wild-type (WT) mice after infections. Compared with infected WT mice, infected Gal-3KO mice exhibited less inflammation in the lungs and reduced IL-1β levels in bronchoalveolar lavage fluid. In addition, the bone marrow–derived macrophages (BMMs) from Gal-3KO mice exhibited reduced oligomerization of apoptosis-associated speck-like proteins containing caspase-associated recruitment domains and secreted less IL-1β compared with BMMs from WT mice. However, similar levels of the inflammasome component of nucleotide oligomerization domain–like receptor protein 3 (NLRP3) were observed in two genotypes of BMMs. Co-immunoprecipitation data indicated galectin-3 and NLRP3 interaction in BMMs infected with H5N1. An association was also observed between galectin-3 and NLRP3/apoptosis-associated speck-like proteins containing caspase-associated recruitment domain complex. Combined, our results suggest that endogenous galectin-3 enhances the effects of H5N1 infection by promoting host inflammatory responses and regulating IL-1β production by macrophages via interaction with NLRP3.

Original languageEnglish (US)
Pages (from-to)1031-1042
Number of pages12
JournalAmerican Journal of Pathology
Volume188
Issue number4
DOIs
StatePublished - Apr 1 2018
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Chen, Y. J., Wang, S. F., Weng, I. C., Hong, M. H., Lo, T. H., Jan, J. T., Hsu, L. C., Chen, H. Y., & Liu, F-T. (2018). Galectin-3 Enhances Avian H5N1 Influenza A Virus–Induced Pulmonary Inflammation by Promoting NLRP3 Inflammasome Activation. American Journal of Pathology, 188(4), 1031-1042. https://doi.org/10.1016/j.ajpath.2017.12.014