Mechanisms of persistence, innate immune activation and immunomodulation by the gastric pathogen Helicobacter pylori

Abstract

The gastric bacterium Helicobacter pylori efficiently evades innate immune detection and persistently colonizes its human host. Understanding the genetic determinants that H. pylori uses to establish and maintain persistence, along with their cellular targets, is key to our understanding of the pathogenesis of this extraordinarily successful bacterial colonizer of the human stomach. This review highlights recent advances in elucidating innate immune recognition of H. pylori, its interactions with myeloid cells and the consequences that this very local infection has for immune responses at extragastric sites in models of allergy, autoimmunity and parasitic infection. The human-specific, gram-negative gastric colonizer and carcinogen H. pylori represents the prototype of a persistent bacterial pathogen. It is transmitted during early childhood, typically from mother to infant, and is believed to persist in its human host from the cradle to the grave. The tremendous success of H. pylori in infecting and colonizing half of the world's population, and in continuously accompanying humans since they migrated out of Africa over 60000 years ago, can largely be attributed to its ability to manipulate the host immune system to its own advantage, and to thereby ensure its own persistence and chronicity. In his final years as an active PI, Stanley Falkow increasingly recognized the need to understand bacterial persistence strategies as a prerequisite of understanding the pathogenesis of chronic bacterial infections, and, inspired in large part by Denise Monack's work on Salmonella persistence, many of our discussions at the time revolved around this topic. Multiple labs have since made important contributions to our understanding of innate immune detection of H. pylori, the types and polarization of adaptive immune responses that ensue, the ability of H. pylori to skew such immune responses to its advantage, and its ability to manipulate the host immune system with far-reaching, even systemic consequences. This review attempts to cover some of these topics, with a particular focus on the most recent contributions by researchers in the field.

Helicobacter pylori Related Diseases and Osteoporotic Fractures (Narrative Review)

“…Urease, in addition to its role in acid neutralization, contributes to H.p. pathogenicity by production ammonia (disrupts cell junctions and damages epithelium) and reactive oxygen species (ROS), activating lipoxygenase, inducing angiogenesis, hypoxia-induced factor and apoptosis [ 26 , 27 , 28 , 29 , 30 ]. The helical shape and flagella, two factors responsible for bacterial mobility, also contribute to colonization and persistence of the infection (allow H.p.…”

“…H.p. induces activation of most components of innate (epithelial, neutrophil, macrophage and dendritic cells) and adaptive immunity (B and T cells) [ 30 , 33 , 34 , 35 ]. H.p., especially with specific virulent strains, in addition to a local reaction results in systemic low-grade inflammation [ 36 , 37 , 38 ].…”

Inhibition of Type IV Secretion Activity and Growth of Helicobacter pylori by Cisplatin and Other Platinum Complexes

“…The Cag type IV secretion system builds up a remarkable multiprotein complex composed of roughly 20 different proteins, which spans the bacterial inner and outer membranes and is able to translocate the bacterial CagA protein into the cytoplasm of gastric cells (Fischer, 2011;Chung et al, 2019;Hu et al, 2019). Furthermore, the Cag type IV secretion system is involved in inducing a strong proinflammatory response in gastric epithelial cells via NF-kB signaling (Zhang et al, 2020). The presence of the cag pathogenicity island increases the risk of developing severe disease, particularly of gastric adenocarcinoma (Wroblewski et al, 2010).…”

Antibacterial activity of Zn-loaded Cuban zeolite against Helicobacter pylori in comparison to its Na-loaded and unmodified counterparts

“…The gram-negative bacterium Helicobacter pylori is very well adapted for colonization of the human stomach, can be found in about half of the human population and seems to belong to the normal human microbiota (Cover and Blaser 2009). This microorganism learned in the evolution of mankind to manipulate the host immune system to its own advantage through unique biochemical mechanisms to persist chronically (Zhang et al 2020). Due to the interactions between host and cohabitant an overwhelming level of this bacterium increases the risk of chronic gastritis, peptic ulcer and gastric cancer (Abadi and Yamaoka 2018).…”

“…Due to the interactions between host and cohabitant an overwhelming level of this bacterium increases the risk of chronic gastritis, peptic ulcer and gastric cancer (Abadi and Yamaoka 2018). On the other hand, several studies report that especially in young people H. pylori infection reduces allergen-specific immune responses like asthma and other allergic diseases, as well as atopy risk (Hojsak and Kolaček 2014;Taye et al 2017;Fouda et al 2018;Zhang et al 2020). Furthermore, the prevalence of an autoimmune disease like multiple sclerosis (MS) is significantly lower in patients infected with H. pylori than in uninfected persons, suggesting that this bacterium acts as a protective factor against the development of MS (Jaruvongvanich et al 2016).…”