Development of the human gut microbiota commences at birth, with bifidobacteria being among the first colonizers of the sterile newborn gastrointestinal tract. To date, the genetic basis of Bifidobacterium colonization and persistence remains poorly understood. Transcriptome analysis of the Bifidobacterium breve UCC2003 2.42-Mb genome in a murine colonization model revealed differential expression of a type IVb tight adherence (Tad) pilus-encoding gene cluster designated "tad 2003 ." Mutational analysis demonstrated that the tad 2003 gene cluster is essential for efficient in vivo murine gut colonization, and immunogold transmission electron microscopy confirmed the presence of Tad pili at the poles of B. breve UCC2003 cells. Conservation of the Tad pilus-encoding locus among other B. breve strains and among sequenced Bifidobacterium genomes supports the notion of a ubiquitous pili-mediated host colonization and persistence mechanism for bifidobacteria.fimbriae | probiotic | prebiotic | genomics

The IL-1 family of cytokines currently comprises of seven ligands with pro-inflammatory activity (IL-1α and IL-1β, IL-18, IL-33, IL-36α, IL-36β, IL-36γ) as well as two ligands with anti-inflammatory activity (IL-37, IL-38). These cytokines are known to play a key role in modulating both the innate and adaptive immunes response, with dysregulation linked to a variety of autoimmune and inflammatory diseases. Given the increasing appreciation of the link between inflammation and cancer, the role of several members of this family in the pathogenesis of cancer has been extensively investigated. In this review, we highlight both the pro- and anti-tumorigenic effects identified for almost all members of this family, and explore potential underlying mechanisms accounting for these divergent effects. Such dual functions need to be carefully assessed when developing therapeutic intervention strategies targeting these cytokines in cancer.

Elevated expression of COX-2 and increased levels of PGE 2 are found in numerous cancers and are associated with tumour development and progression. Although epidemiological, clinical and preclinical studies have shown that the inhibition of PGE 2 synthesis through the use of either non-steroidal anti-inflammatory drugs (NSAIDs) or specific COX-2 inhibitors (COXibs) has the potential to prevent and treat malignant disease, toxicities due to inhibition of COX-2 have limited their use. Thus, there is an urgent need for the development of strategies whereby COX-2 activity may be reduced without inducing any side effects. The biological effects of PGE 2 are mediated by signalling through four distinct E-type prostanoid (EP) receptors -EP 1 , EP 2 , EP 3 and EP 4 . In recent years, extensive effort has gone into elucidating the function of PGE 2 and the EP receptors in health and disease, with the goal of creating selective inhibitors as a means of therapy. In this review, we focus on PGE 2 , and in particular on the role of the individual EP receptors and their signalling pathways in neoplastic disease. As knowledge concerning the role of the EP receptors in cancer grows, so does the potential for exploiting the EP receptors as therapeutic targets for the treatment of cancer and metastatic disease. AbbreviationsCOXibs, specific COX-2 inhibitors; EMT, epithelial-mesenchymal transition; NSAIDs, non-steroidal anti-inflammatory drugs; YB-1, Y-box binding protein 1 BJP IntroductionInflammation has been established in recent years as playing a major role in cancer, with cancer-promoting inflammation an enabling characteristic underlying many, if not all, of the six hallmarks of cancer (Hanahan and Weinberg, 2011). In some cancers, the inflammatory conditions precede the development of malignancy, for example, ulcerative colitis is a major risk factor for colon cancer (Gupta et al., 2007). Alternatively, oncogenic mutations can drive tumour-promoting inflammation in tumours that are epidemiologically unrelated to overt inflammatory conditions (Del Prete et al., 2011). One key inflammatory mediator deregulated in many cancers is the COX enzyme, COX-2 (Janakiram and Rao, 2014). COX-2 expression has been shown in many cancers to be inversely associated with patient survival (Gallo et al., 2002;Peng et al., 2013;Sicking et al., 2014), with epidemiological studies suggesting that regular aspirin use decreases colorectal cancer incidence and mortality through the inhibition of COX-2 (Chan et al., 2009). Thus, drugs that target COX-2 may have chemopreventative or chemotherapeutic functions. Although drugs that target the COX enzymes have entered the clinic, albeit for different diseases, inhibition of COX-2 using either non-steroidal anti-inflammatory drugs (NSAIDs) or specific COX-2 inhibitors (COXibs) is associated with various side effects including gastric ulceration and myocardial infarction (Ranger, 2014). Such toxicities have limited their clinical applications. Dysregulation of COX-2 leads to elevated levels of its princ...

Fas ligand (FasL) has become an enigmatic molecule: some evidence indicates that it contributes to immune privilege in tissues and tumors, whereas other data demonstrates that FasL can elicit inflammation. New findings may begin to reconcile the paradoxical effects of FasL.

Listeria monocytogenes is a Gram-positive bacterium that can cause septicemia and meningitis. TLRs are central receptors of the innate immune system that drive inflammatory responses to invading microbes such as L. monocytogenes. Although intestinal epithelial cells (IECs) represent the initial point of entry used by L. monocytogenes for infection, the innate immune response to L. monocytogenes in these cells has been poorly characterized to date. The aim of this study was to determine which TLRs are involved in mediating the immune response to L. monocytogenes in IECs. We performed an RNA interference screen of TLRs 1–10 in the HT-29 IEC cell line and observed the most significant reduction in chemokine output following silencing of TLR10. This effect was also observed in the macrophage cell line THP-1. The chemokines CCL20, CCL1, and IL-8 were reduced following knockdown of TLR10. Silencing of TLR10 resulted in increased viability of L. monocytogenes in both HT-29 and THP-1 cells. TLR10 was found to be predominantly expressed intracellularly in epithelia, and activation required viable L. monocytogenes. NF-κB activation was seen to require TLR2 in addition to TLR10. Taken together, these data indicate novel roles for TLR10 in sensing pathogenic infection in both the epithelium and macrophages and have identified L. monocytogenes as a source of ligand for the orphan receptor TLR10.