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Helicobacter pylori triggers gastric inflammation by injecting peptidoglycan from its cell wall into epithelial cells, where it is recognized by an intracellular pathogen recognition molecule, researchers report in Nature Immunology this week.
Richard Ferrero and colleagues at Institut Pasteur in France note in their paper that H. pylori strains carrying the cag pathogenicity island (cagPAI) are known to be more often associated with severe gastric inflammation and its pathogenic consequences in humans, but the mechanism underlying the link had been poorly understood.
Because H. pylori doesn't invade epithelial cells but lives outside among a wide range of commensal bacteria, "the question was, if together with commensal bacteria you have bacteria that are not commensal but pathogens, how are they recognized?" said Rino Rappuoli, from Chiron Research Center, Siena, Italy, who wrote an accompanying News and Views article.
The answer, Ferrero told The Scientist, is that "H. pylori is a noninvasive bacterium that is capable of triggering what is essentially an intracellular molecule." Strains carrying cagPAI deliver peptidoglycan to the epithelial cells, where it is recognized by the pathogen recognition molecule Nod1, he said.
"Nod1 has similarities to a whole family of proteins, some of which are found in plants and have been shown to be important in host defense of the plant against microbial invasion or infection," Ferrero added.
The work has relevance beyond H. pylori. It may be important for bacteria that use type III secretion systems—very similar in mechanism to type IV, explained Rappuoli, who was not involved in the study. "We didn't know how they could be present in the same place as commensals and [also] stimulate the innate immunity. And now we can speculate that they also do the same thing [as H. pylori]."
"It's interesting biology because the organism is signaling the host by purposefully—adaptively—injecting pieces of its own cell wall into the [host] cells. So one of the questions that raises is, why is H. pylori doing that?" said Martin J. Blaser, from New York University School of Medicine.
The question should be viewed in the context of H. pylori as an often lifelong infection, said Blaser, who was not involved in the study. "I think that part of the message here is that H. pylori has co-evolved with humans, and it's evolved in a way that provides for persistence of the bacterium over decades."
The work also extends understanding of the importance of Nod1, Blaser went on. "In recent years, we've been thinking about Nod1 in terms of invasive organisms. H. pylori is an organism that lives in the lumen, although it's not exactly a luminal organism because of its attachment and its use of the type IV system. So we're extending the zone of innate immunity to organisms that are predominantly luminal."
There are two hypotheses for why the bacterium should secrete something that triggers the inflammatory response, according to Ferrero. Either the interaction between the peptidoglycan and Nod1 is beneficial in some way to the bacterium or, alternatively, the presence of the cagPAI per se may be important for other functions involving colonisation or persistence, he said.
"Personally I think this [latter] is the less likely scenario, but at the moment we have no clear idea as to why the bacterium would be inducing this response via Nod1," Ferrero said.
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