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Galectin-3 Enhances Avian H5N1 Influenza A Virus-Induced Pulmonary Inflammation by Promoting NLRP3 Inflammasome Activation #MMPMID29366678
Chen YJ; Wang SF; Weng IC; Hong MH; Lo TH; Jan JT; Hsu LC; Chen HY; Liu FT
Am J Pathol 2018[Apr]; 188 (4): 1031-1042 PMID29366678show ga
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 beta-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-1beta 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-1beta 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-1beta production by macrophages via interaction with NLRP3.
|Animals[MESH]
|Birds/*virology[MESH]
|CARD Signaling Adaptor Proteins/metabolism[MESH]
|Dogs[MESH]
|Galectin 3/*metabolism[MESH]
|HEK293 Cells[MESH]
|Humans[MESH]
|Influenza A Virus, H5N1 Subtype/*physiology[MESH]
Am+J+Pathol 2018 ; 188 (4): 1031-1042
