Bacterial chemotaxis modulates host cell apoptosis to establish a T-helper cell, type 17 (Th17)-dominant immune response in Helicobacter pylori infection

Abstract

The host inflammatory response to chronic bacterial infections often dictates the disease outcome. In the case of the gastric pathogen Helicobacter pylori, host inflammatory responses result in outcomes that range from moderate and asymptomatic to more severe with concomitant ulcer or cancers. It was found recently that H. pylori chemotaxis mutants (Che − ), which lack directed motility but colonize to nearly wild-type levels, trigger less host inflammation. We used these mutants to observe host immune responses that resulted in reduced disease states. Here we report that these mutants are defective for early gastric recruitment of CD4 + T cells compared with wild-type infection. Furthermore, Che − mutant infections lack the Thelper cell, type 17 (Th17) component of the immune response, as measured by cytokine mRNA levels in gastric tissue via intracellular cytokine staining and immunofluorescence. We additionally find that a Che − mutant infection results in significantly less host cell apoptosis than does wild-type infection, in accordance with previous observations that T-helper cell, type 17 responses in Citrobacter rodentium infections are driven by concomitant bacterial and apoptotic cell signals. We propose that bacterial chemotaxis allows H. pylori to access a particular host niche that allows the bacteria to express or deliver proapoptotic host cell factors. This report indicates that chemotaxis plays a role in enhancing apoptosis, suggesting bacterial chemotaxis systems might serve as therapeutic targets for infections whose symptoms arise from host cell apoptosis and tissue damage.T regulatory cells | adaptive immunity | pathogenesis

Role of Energy Sensor TlpD of Helicobacter pylori in Gerbil Colonization and Genome Analyses after Adaptation in the Gerbil

“…All of these stimuli very likely influence bacterial energy metabolism and would need to be balanced continuously by the TlpD-mediated bacterial behavior to locally optimize bacterial distribution and persistence. H. pylori colonization provokes a gastric inflammatory and oxidative stress response, and this response is increased for cagPAI-positive strains, mainly by the direct interaction of the bacteria with the gastric epithelium, as has been observed in humans, mice, and gerbils (1,36,51,(70)(71)(72)(73). Our in vitro assays using paraquat suggested an intrinsically reduced fitness of the tlpD mutants in the presence of oxidative stress, which was partially reverted by TlpD complementation.…”

The Degree of Helicobacter pylori-Triggered Inflammation Is Manipulated by Preinfection Host Microbiota

“…Such species remain to be discovered, however. It is tempting to speculate that the reduced inflammatory response we observe early postinoculation would drive conditions that would result in reduced inflammation long term; other work has demonstrated that the CD4 response at 4 weeks accurately reflects the long-term H. pylori inflammatory response (26). However, future experiments will need to examine the enduring effects on the inflammatory state.…”

“…3B and C). We chose these cells as they are known to arrive relatively early in response to H. pylori infection and also are reflective of the host response at later time points (26,35). As expected, normal mice developed a CD4 ϩ response to H. pylori infection that was significantly above that of uninfected mice (Fig.…”

Association of Pneumococcal Carriage and Expression of Foxp3+ Regulatory T Cells and Th17 Cells in the Adenoids of Children

“…It has recently been shown that Th17 cells and IL-17 function during infections to eliminate pathogens such as Helicobacter pylori, Mycobacterium tuberculosis and Toxoplasma, etc. [7,8] . The number and activation of CD4+ T cells, and especially Th17 cells, may adversely impact the cytokine network and a patient's recovery from pneumococcal pneumonia, as well as their ability to eliminate streptococci [9,10] .…”