Critical involvement of pneumolysin in production of interleukin-1 alpha and caspase-1-dependent cytokines in infection with Streptococcus pneumoniae in vitro: a novel function of pneumolysin in caspase-1 activation

Shereen Shoma and Kohsuke Tsuchiya and Ikuo Kawamura and Takamasa Nomura and Hideki Hara and Ryosuke Uchiyama and Sylvia Daim and Masao Mitsuyama (2008) Critical involvement of pneumolysin in production of interleukin-1 alpha and caspase-1-dependent cytokines in infection with Streptococcus pneumoniae in vitro: a novel function of pneumolysin in caspase-1 activation. Infection and Immunity, 76. pp. 1547-1557. ISSN 0019-9567

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URL: http://iai.asm.org/content/76/4/1547.full

Abstract

Pneumolysin is a pore-forming cytolysin known as a major virulence determinant of Streptococcus pneumoniae. This protein toxin has also been shown to activate the Toll-like receptor 4 (TLR4) signaling pathway. In this study, a mutant S. pneumoniae strain deficient in pneumolysin (Δply) and a recombinant pneumolysin protein (rPLY) were constructed. Upon infection of macrophages in vitro, the ability to induce the production of interleukin-1α (IL-1α), IL-1β, and IL-18 was severely impaired in the Δply mutant, whereas there was no marked difference in the induction of tumor necrosis factor alpha (TNF-α) and IL-12p40 between the wild type and the Δply mutant of S. pneumoniae. When macrophages were stimulated with rPLY, the production of IL-1α, IL-1β, and IL-18 was strongly induced in a TLR4-dependent manner, whereas lipopolysaccharide, a canonical TLR4 agonist, hardly induced these cytokines. In contrast, lipopolysaccharide was more potent than rPLY in inducing the production of TNF-α, IL-6, and IL-12p40, the cytokines requiring no caspase activation. Activation of caspase-1 was observed in macrophages stimulated with rPLY but not in those stimulated with lipopolysaccharide, and the level of activation was higher in macrophages infected with wild-type S. pneumoniae than in those infected with the Δply mutant. These results clearly indicate that pneumolysin plays a key role in the host response to S. pneumoniae, particularly in the induction of caspase-1-dependent cytokines.

Item Type:	Article
Keyword:	Pneumolysin , Streptococcus pneumoniae , Pore-forming cytolysin
Subjects:	R Medicine > R Medicine (General) > R5-920 Medicine (General)
Department:	FACULTY > Faculty of Medicine and Health Sciences
Depositing User:	SITI AZIZAH BINTI IDRIS -
Date Deposited:	24 Sep 2021 09:10
Last Modified:	24 Sep 2021 09:10
URI:	https://eprints.ums.edu.my/id/eprint/29305

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