Pathogenesis and host response of Helicobacter pylori

The 5th International Workshop on Pathogenesis and Host Response in Helicobacter Infections was held in Elsinore, Denmark, 4–7 July, 2002.     

Pathogenesis and host response of Helicobacter pylori

The 5th International Workshop on Pathogenesis and Host Response in Helicobacter Infections was held in Elsinore, Denmark, 4–7 July, 2002.     

Tuberculosis: Pathogenesis,immune response,and host genetics

Tuberculosis is a chronic infectious disease that predominantly affects the lungs. The hallmark of tuberculosis infection is the formation of granulomas in the vicinity of infectious foci. Tuberculous granulomas are highly organized bodies with a complex cell composition and well-orchestrated biochemical pathways. Granuloma development plays a dual role. The process restricts the infection dissemination and forms a battlefield for protective immunity but simultaneously may compromise the lung function, threatening host health. The susceptibility to the infection per se, the degree of lung failure, and disease severity are under genetic control. Tuberculosis genetics is complex and poorly understood, but current knowledge indicates that intracellular infections are controlled by a network of biochemical reactions, many of which were not suspected to be involved until recently.     

Neoparamoebic gill infections: host response and physiology in salmonids

Amoebic gill diseases (AGD) caused primarily by the amphizoic Neoparamoeba spp. have been identified as significant to fish health in intensive aquaculture. These diseases have consequently received significant attention with regard to disease pathophysiology. Neoparamoeba perurans has been putatively identified as the aetiological agent in salmonids, with other species such as turbot Psetta maxima and sea bass Dicentrarchus labrax also affected. Similarly, Neoparamoeba spp. have also been identified in co‐infections with other gill diseases in salmonids. While infection of the gills results in an acute multifocal hyperplastic host response, reduced gill surface area and increased mucous cell densities, ion regulation and respiration in terms of blood gasses are only marginally affected. This may be partially attributed to reserve respiratory capacity and a reduction in mucous viscosity allowing for a greater flushing of the gill, so reducing the gill mucus boundary layer. Clinical and acute infections result in significant cardiovascular compromise with increases in aortic blood pressure, and systemic vascular resistance in Atlantic salmon, Salmo salar, which are not seen in rainbow Oncorhynchus mykiss and brown trout Salmo trutta. Increases in vascular resistance appear to be due to vascular constriction potentially reducing blood flow to the heart in compromised fishes, the overall effect being to lead to a compensatory tissue remodelling and change in cardiac shape in chronically infected fishes. The combined effect of reduced gill surface area and cardiovascular compromise leads to a significant reduction in swimming performance and increases in the routine metabolic rate that lead to an increase in the overall metabolic cost of disease.     

The host type I interferon response to viral and bacterial infections

Type I interferons (IFN) are well studied cytokines with anti-viral and immune-modulating functions. Type I IFNs are produced following viral infections, but until recently, the mechanisms of viral recognition leading to IFN production were largely unknown. Toll like receptors (TLRs) have emerged as key transducers of type I IFN during viral infections by recognizing various viral components. Furthermore, much progress has been made in defining the signaling pathways downstream of TLRs for type I IFN production. TLR7 and TLR9 have become apparent as universally important in inducing type I IFN during infection with most viruses, particularly by plasmacytoid dendritic cells. New intracellular viral pattern recognition receptors leading to type I IFN production have been identified. Many bacteria can also induce the up-regulation of these cytokines. Interestingly, recent studies have found a detrimental effect on host cells if type Ⅰ IFN is produced during infection with the intracellular gram-positive bacterial pathogen, Listeria monocytogenes. This review will discuss the recent advances made in defining the signaling pathways leading to type I IFN production.     

Pathogenesis of Helicobacter pylori infection

Helicobacter pylori infections and clinical outcome are dependent on sophisticated interactions between the bacteria and its host. Crucial bacterial factors associated with pathogenicity comprise a type IV secretion system encoded by the cag pathogenicity island, the effector protein CagA, the vacuolating cytotoxin (VacA), peptidoglycan, lipopolysaccharide (LPS), γ-glutamyl transpeptidase (GGT), protease HtrA, and the adhesins BabA, SabA, and others. The high number of these factors and allelic variation of the involved genes generates a highly complex scenario and reveals the difficulties in testing the contribution of each individual factor. Much effort has been put into identifying the molecular mechanisms associated with H. pylori-associated pathogenesis using human primary tissues, Mongolian gerbils, transgenic, knockout, and other mice as well as in vitro cell model systems. Interactions between bacterial factors and host signal transduction pathways seem to be critical for mediating the induction of pathogenic downstream processes and disease development. In this review article, we discuss the most recent progress in this research field.     

Pathogenesis of Helicobacter pylori Infection

Helicobacter pylori induces chronic inflammation of the gastric mucosa, but only a proportion of infected individuals develop peptic ulcer disease or gastric carcinoma. Reasons underlying these observations include differences in bacterial pathogenicity as well as in host susceptibility. Numerous studies published in the last year provided new insight into H. pylori virulence factors, their interaction with the host and consequences in pathogenesis. These include the role of bacterial genetic diversity in host colonization and persistence, outer membrane proteins and modulation of adhesin expression, new aspects of VacA functions, and CagA and its phosphorylation-dependent and -independent cellular effects. This article will also review the recent novel findings on the interactions of H. pylori with diverse host epithelial signaling pathways and events involved in the initiation of carcinogenesis, including genetic instability and dysregulation of DNA repair.     

Pathogenesis of Helicobacter pylori infection

Helicobacter pylori infections are thought to eventually lead to symptoms as a result of the long-lasting interactions between the bacterium and its host. Mechanisms that allow this bacterium to cause a life-long infection involve modulation of both the immune response and host cellular processes. Last year many novel findings that improve our knowledge on how H.?pylori virulence factors interact with the host were reported, but because of space limitations we can only discuss a limited number of these studies. Among those are studies on the genetic variation of genes encoding outer membrane proteins and the mimicry of host antigens, factors that alter host-cell metabolism and factors that modulate the host's immune response.     

Pathogenesis of Helicobacter pylori Infection

The clinical outcome of Helicobacter pylori infection is determined by a complex scenario of interactions between the bacterium and the host. The main bacterial factors associated with colonization and pathogenicity comprise outer membrane proteins including BabA, SabA, OipA, AlpA/B, as well as the virulence factors CagA in the cag pathogenicity island ( cag PAI) and the vacuolating cytotoxin VacA. The multitude of these proteins and allelic variation makes it extremely difficult to test the contribution of each individual factor. Much effort has been put into identifying the mechanism associated with H. pylori -associated carcinogenesis. Interaction between bacterial factors such as CagA and host signal transduction pathways seems to be critical for mediating the induction of membrane dynamics, actin-cytoskeletal rearrangements and the disruption of cell-to-cell junctions as well as proliferative, pro-inflammatory and antiapoptotic nuclear responses. An animal model using the Mongolian gerbil is a useful system to study the gastric pathology of H. pylori infection.     

Pathogenesis of Helicobacter pylori Infection

Although Helicobacter pylori infection is highly prevalent in the global human population, the majority of infected individuals remain asymptomatic. A complex combination of host, environmental, and bacterial factors are considered to determine susceptibility and severity of outcome in the subset of individuals that develop clinical disease. These factors collectively determine the ability of H.?pylori to colonize the gastric mucosa and profoundly influence the nature of the interaction that ensues. Many studies over the last year provide new insight into H.?pylori virulence strategies and the activities of critical bacterial determinants that modulate the host environment. These latter include the secreted proteins CagA and VacA and adhesins BabA and OipA, which directly interact with host tissues. Observations from several studies extend the functional repertoire of CagA and the cag type IV secretion system in particular, providing further mechanistic understanding of how these important determinants engage and activate host signalling pathways important in the development of disease.