Roles of the bacterial cell wall and capsule in induction of tumor necrosis factor alpha by type III group B streptococci

Abstract

Group B streptococci (GBS) are the major cause of sepsis and fatal shock in neonates in the United States. The precise role of tumor necrosis factor alpha (TNF-␣) in the development of human GBS sepsis has not been defined; however, whole GBS have been shown to induce the production of this inflammatory cytokine. We sought to determine which bacterial cell wall components of GBS are responsible for triggering TNF-␣ production. Human cord blood monocytes were stimulated with encapsulated (COH1) or unencapsulated (COH1-13) whole type III GBS or with purified bacterial components, including type III capsular polysaccharide (III-PS), group B polysaccharide (GB-PS), lipoteichoic acid (LTA), or peptidoglycan (PG). Lipopolysaccharide from Escherichia coli served as a control. Supernatants were harvested at specific timed intervals, and TNF-␣ levels were measured by enzyme-linked immunosorbent assay. Monocytes exposed to COH1 and COH1-13 induced similar amounts of TNF-␣. III-PS, GB-PS, LTA, and PG each induced TNF-␣ in a time-and concentration-dependent manner. However, TNF-␣ release was significantly greater after stimulation by the GB-PS or PG than after stimulation by III-PS or LTA (P < 0.05). Our findings indicate that GB-PS and PG are the bacterial cell wall components primarily evoking TNF-␣ release. These, alone or in concert with other factors, may be responsible for septic shock accompanying GBS sepsis.

A pivotal role for theStreptococcus iniaeextracellular polysaccharide in triggering proinflammatory cytokines transcription and inducing death in rainbow trout

“…Despite great efforts, results are often inconclusive or contradictory. For example, while some works clearly suggest that purified type and/or group‐specific GBS polysaccharides induce considerable TNF‐α secretion, (Vallejo et al , 1996; Cuzzola et al , 2000), in vivo data often do not support these results (Williams et al , 1993; Ling et al , 1995). Similar findings were described in the case of S. pneumoniae (Tuomanen et al , 1985).…”

“…Current opinion perceives sepsis as the consequence of the excessive activation of the innate immune system through Toll‐like receptors, ensuing in an uncontrolled release of multiple proinflammatory and anti‐inflammatory cytokines that are largely responsible for the experimental and clinical symptoms of sepsis and septic shock (Bhakdi et al , 1991; Anderson et al , 1992; Bone, 1993; Cavaillon, 1995; Wenzel et al , 1996; Medzhitov & Janeway, 1997a, b; Gao et al , 1999; Opal & Cohen, 1999; Sriskandan & Cohen, 1999; Ashare et al , 2005; Bozza et al , 2007). Although heterogeneous bacterial components [including bacterial wall components, peptidoglycan, lipoteichoic acid (LTA) and bacterial DNA (Heumann et al , 1994; Mattsson et al , 1994; de Kimpe et al , 1995; Timmerman et al , 1995; Vallejo et al , 1996; Sparwasser et al , 1997; Kengatharan et al , 1998; Gao et al , 1999; Opal & Cross, 1999)], commonly termed ‘pathogen‐associated molecular pattern’ molecules (Medzhitov & Janeway, 1997a, b) have been implicated as initiating these responses, it is widely accepted that, in Gram‐negative bacterial sepsis, the pathophysiology basically involves an early and excessive release of lipopolysaccharide (LPS)‐induced cytokines (Suffredini et al , 1989; Danner et al , 1991). It is also believed that, among the various cytokines, tumor necrosis factor‐α (TNF‐α), interleukin‐1β (IL‐1β) and IL‐6 are the pivotal factors, mediating reactions associated with clinical deterioration, multiorgan system failure and death (Waage et al , 1991; Anderson et al , 1992; Beutler & Grau, 1993; Bone, 1993, 1994; Casey et al , 1993; Muller‐Alouf et al , 1994; Wenzel et al , 1996; Silverstein et al , 1997; Okusawa et al , 1998; Cohen & Abraham, 1999).…”

“…Unlike the pathophysiology of shock caused by Gram‐negative bacteria, which has been extensively investigated, comparatively little is known about the pathogenesis of the sepsis and shock induced by Gram‐positive pathogens and, despite the fact that several Gram‐positive bacterial components have been shown to trigger cytokine release by monocytes (Bone, 1993, 1994; Heumann et al , 1994; Mattsson et al , 1994; Timmerman et al , 1995; Vallejo et al , 1996; Kengatharan et al , 1998), a common pattern of bioactive molecules has not been defined. The conviction that LTA is the unequivocal counterpart of LPS in terms of pathogenesis of Gram‐positive bacteria (Ginsburg, 2002) is also wavering (Nealon & Mattingly, 1985; Bhakdi et al , 1991; Vallejo et al , 1996; Han et al , 2003). In some instances (i.e.…”

“…GAS), a number of different active substances that can initiate sepsis have been identified (Bone, 1993; Curtis, 1996). It therefore appears that the triggering molecules of Gram‐positive bacteria are heterogeneous, and that these pathogens lack a common single LPS comparable mediator capable of initiating the entire cascade of inflammatory cytokines (Vallejo et al , 1996). Likewise, the cytokine network that accompanies Gram‐positive sepsis is uncertain, with relatively few studies suggesting the equivalent involvement of cytokines in Gram‐positive and Gram‐negative sepsis (Wakabayashi et al , 1991; Timmerman et al , 1995), while other evidence substantiates the possibility of a kinetically and qualitatively different machinery (Anderson et al , 1992; Muller‐Alouf et al , 1994; Silverstein et al , 1997; Cohen & Abraham, 1999).…”

Increased Antibody Production against Gut‐Colonizing Escherichia coli in the Presence of the Anaerobic Bacterium Peptostreptococcus

“…It is possible that products derived from Gram-positive bacteria may interact with antigen-presenting cells and promote them to present E. coli antigens more efficiently to T and/or B cells, by increasing the production of stimulatory cytokines and/ or costimulatory molecules. Peptidoglycans are known inducers of tumour necrosis factor-a (TNF-a) and have been implicated in the potent immunogenicity of Mycobacterium tuberculosis cell wall components [20,21]. TNF-a and granulocyte-macrophage colony-stimulating factor (GM-CSF), both of which may be induced by bacterial products, have been shown to increase the maturation of dendritic cells in mouse Peyer's patches, leading to a more efficient antigen presentation to T cells [22].…”