Cytokine responses during mucosal infections: role in disease pathogenesis and host defence

Svanborg, Catharina; Godaly, Gabriela; Hedlund, Maria

doi:10.1016/s1369-5274(99)80017-4

Cited by 171 publications

(123 citation statements)

References 55 publications

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“…In this setting, recruited neutrophils use much of their granule contents, including BPI, to mediate intracellular cytotoxicity after phagocytosis of the invading bacteria. In addition, recruited and activated neutrophils release some of their granule contents into the surrounding inflammatory fluid [83][84][85][86]. The released proteins may contribute to containment and killing of extracellular bacteria that have exceeded or evaded/resisted the phagocytic capacity of the neutrophils and also to elimination of bioactive bacterial remnants [87,88].…”

Section: Bpi Actions During Host: Gnb Interactionsmentioning

confidence: 99%

The bactericidal/permeability-increasing protein (BPI) in infection and inflammatory disease

Schultz

Weiss

2007

Clinica Chimica Acta

111

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Gram-negative bacteria (GNB) and their endotoxin present a constant environmental challenge. Endotoxins can potently signal mobilization of host defenses against invading GNB but also potentially induce severe pathophysiology, necessitating controlled initiation and resolution of endotoxin-induced inflammation to maintain host integrity. The bactericidal/permeability-increasing protein (BPI) is a pluripotent protein expressed, in humans, mainly neutrophils. BPI exhibits strong anti-microbial activity against GNB and potent endotoxin-neutralizing activity. BPI mobilized with neutrophils in response to invading GNB can promote intracellular and extracellular bacterial killing, endotoxin neutralization and clearance, and delivery of GNB outer membrane antigens to dendritic cells. Tissue expression by dermal fibroblasts and epithelia could further amplify local levels of BPI and local interaction with GNB and endotoxin, helping to constrain local tissue infection and inflammation and prevent systemic infection and systemic inflammation. This review article focuses on the structural and functional properties of BPI with respect to its contribution to host defense during GNB infections and endotoxin-induced inflammation and the genesis of auto-antibodies against BPI that can blunt BPI activity and potentially contribute to chronic inflammatory disease.

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Section: Bpi Actions During Host: Gnb Interactionsmentioning

confidence: 99%

The bactericidal/permeability-increasing protein (BPI) in infection and inflammatory disease

Schultz

Weiss

2007

Clinica Chimica Acta

111

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“…Interleukin (IL)-2 KO, IL-10 KO, T-cell receptor ␤/p53 DKO, or tumor growth factor ␤1/Rag-2 DKO mice, when maintained under germ-free (GF) conditions, fail to develop severe inflammation, as well as small intestinal or colonic cancers that often occur when those animals are raised under conventional housing conditions (3)(4)(5)(6). Because microflora can modulate epithelial cell signaling for immune reactions (7)(8)(9), this may explain the susceptibility of these immune-compromised mice to the development of IBD. Because GPX-DKO mice have an intact immune system at the outset of these studies, the role of microflora on the subsequent development of any pathological condition in these mice was unclear.…”

Section: Introductionmentioning

confidence: 99%

Bacteria-Induced Intestinal Cancer in Mice with DisruptedGpx1andGpx2Genes

Chu

Esworthy

Chu³

et al. 2004

Cancer Research

273

217

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Two glutathione peroxidase (GPX) isozymes, GPX-1 and GPX-2 (GPX-GI), are the major enzymes that reduce hydroperoxides in intestinal epithelium. We have previously demonstrated that targeted disruption of both the Gpx1 and Gpx2 genes (GPX-DKO) results in a high incidence of ileocolitis in mice raised under conventional conditions, which include the harboring of Helicobacter species [non-specific-pathogen-free (non-SPF) conditions]. In this study, we have characterized GPX-DKO mice that have microflora-associated intestinal cancers, which are correlated with increased intestinal pathology/inflammation. We found that GPX-DKO mice raised under germ-free conditions have virtually no pathology or tumors. After colonizing germ-free mice with commensal microflora without any known pathogens (SPF), <9% of GPX-DKO mice develop tumors in the ileum or the colon. However, about one-fourth of GPX-DKO mice raised under non-SPF conditions from birth or transferred from SPF conditions at weaning have predominantly ileal tumors. Nearly 30% of tumors are cancerous; most are invasive adenocarcinomas and a few signet-ring cell carcinomas. On the basis of these results, we conclude that GPX-DKO mice are highly susceptible to bacteria-associated inflammation and cancer. The sensitivity exhibited in these mice suggests that peroxidative stress plays an important role in ileal and colonic pathology and inflammation, which can lead to tumorigenesis.

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“…Epithelial cells appear to serve as sensitive indicators of infection by actively initiating an early host defense response through the secretion of chemokines and proinflammatory cytokines (3,4). Chemokines of the C-X-C and C-C family and proinflammatory cytokines such as IL-1␣, IL-1␤, IL-6, TNF-␣, and GM-CSF produced by epithelial cells recruit immune cells to the epithelial/mucosal surface and help in the activation of macrophages and dendritic cells and the differentiation of effector lymphocytes (3,5,6). Regulatory cytokines involved in the development of Th1/Th2 responses such as IL-12, IFN-␥, and IL-4 are not known to be released from epithelial cells after microbial infection (5).…”

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confidence: 99%

Chlamydia trachomatis Infection of Epithelial Cells Induces the Activation of Caspase-1 and Release of Mature IL-18

Shen

Brunham

2000

The Journal of Immunology

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Th1 cells that secrete IFN-γ are particularly important in protective immunity against intracellular pathogens, including chlamydiae, and IL-18 together with IL-12 are strong inducers of IFN-γ secretion by CD4 T cells. Because epithelial cells are known to synthesize IL-18, we investigated the effects of Chlamydia trachomatis infection of human epithelial cell lines on IL-18 secretion. We confirmed that several human epithelial cell lines constitutively express pro-IL-18 and that C. trachomatis infection causes cells to secrete mature IL-18. This was observed for several different serovars and biovars of C. trachomatis. Chlamydia-induced secretion of IL-18 from epithelial cells was regulated at the posttranscriptional level and was dependent on the activation of caspase-1. IL-1α or other secreted factor(s) from chlamydia-infected epithelial cells as well as chlamydial structural component(s) were not involved in inducing IL-18 secretion. Activation of caspase-1 and increased secretion of mature IL-18 was correlated with chlamydial, but not with host protein synthesis. In contrast to epithelial cell lines, fibroblast cell lines constitutively expressed much lower levels of pro-IL-18 and did not secrete mature IL-18 after chlamydial infection even though caspase-1 was activated. Taken together, the results suggest that a chlamydia-derived factor(s) is essential for the secretion of mature IL-18 through caspase-1 activation in infected epithelial cells.

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Cytokine responses during mucosal infections: role in disease pathogenesis and host defence

Cited by 171 publications

References 55 publications

The bactericidal/permeability-increasing protein (BPI) in infection and inflammatory disease

The bactericidal/permeability-increasing protein (BPI) in infection and inflammatory disease

Bacteria-Induced Intestinal Cancer in Mice with DisruptedGpx1andGpx2Genes

Chlamydia trachomatis Infection of Epithelial Cells Induces the Activation of Caspase-1 and Release of Mature IL-18

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