Novel Virulence Role of Pneumococcal NanA in Host Inflammation and Cell Death Through the Activation of Inflammasome and the Caspase Pathway

is one of most deadly Gram-positive bacterium that causes significant mortality and morbidity worldwide. Intense inflammation and cytotoxicity is a hallmark of invasive pneumococcal disease. Pneumococcal NanA has been shown to exaggerate the production of inflammatory cytokines via unmasking of inhi...

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Bibliographic Details
Published in:Frontiers in cellular and infection microbiology 2021-03, Vol.11, p.613195-613195
Main Authors: Tseng, Yu-Wen, Chang, Chun-Chi, Chang, Yung-Chi
Format: Article
Language:English
Subjects:
caspase
Cellular and Infection Microbiology
inflammasome
NanA
sialidase
Streptococcus pneumoniae
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Summary:is one of most deadly Gram-positive bacterium that causes significant mortality and morbidity worldwide. Intense inflammation and cytotoxicity is a hallmark of invasive pneumococcal disease. Pneumococcal NanA has been shown to exaggerate the production of inflammatory cytokines via unmasking of inhibitory Siglec-5 from its sialyl -ligands. To further investigate the mechanistic role of NanA and Siglec-5 in pneumococccal diseases, we systemically analyzed genes and signaling pathways differentially regulated in macrophages infected with wild type and NanA-deficient pneumococcus. We found that NanA-mediated desialylation impairs the Siglec-5-TLR-2 interaction and reduces the recruitment of phosphatase SHP-1 to Siglec-5. This dysregulated crosstalk between TLR-2 and inhibitory Siglec-5 exaggerated multiple inflammatory and death signaling pathways and consequently caused excessive inflammation and cytotoxicity in the infected macrophage. Collectively, our results reveal a novel virulence role of NanA in pneumococcal pathogenesis and suggest that targeting NanA activity may ameliorate the pneumococcus-mediated inflammation and cytotoxicity in severe invasive pneumococcal diseases.
ISSN:2235-2988
2235-2988
DOI:10.3389/fcimb.2021.613195