The host’s immune system forms small lesions in the gut in response to bacterial infection

Yersinia Bacteria cause a variety of human and animal diseases, the most notorious of which is the plague. Yersinia pestisrelatives, Yersinia pseudotuberculosiscauses gastrointestinal illness and, although not fatal, it naturally infects both mice and humans, making it a useful model for studying its interactions with the immune system.

These two pathogens, and a third relative, Y. enterocoliticaIt affects pigs, and eating infected meat can cause food poisoning.

The plague pathogen is blood-borne and transmitted by infected fleas. Two of her other infections depend on ingestion. However, much of the focus of research in this area is Yersinia in lymphatic tissue rather than in the intestine.new research in pseudotuberculosis Led by a team at Penn’s School of Veterinary Medicine, natural microbiology have shown that in response to infection, the host’s immune system forms small walled lesions in the gut called granulomas. This is the first time that these organized collections of immune cells have been found in the gut. Yersinia Infection.

The team also showed that monocytes, a type of immune cell, maintain these granulomas.Without them, granulomas aggravated and mice Yersinia.

“Our data reveals sites that were previously unappreciated. Yersinia These granulomas form to control bacterial infections in the gut. It shows what you can do.

The findings have implications for the development of new treatments that harness the host’s immune system, says Brodsky.Using the power of immune cells, not only to keep Yersinia But to overcome that defense, they say, it may be possible to eliminate the pathogen entirely.

novel battlefield

Y. Pestis, pseudotuberculosisand Y. enterocolitica Shares sharp ability to evade immune detection.

“All three Yersinia .

In previous studies, Yersinia stimulated the formation of granulomas in the lymph nodes and spleen, but had not seen them in the intestine until Daniel Solovetea, a researcher in Brodsky’s group, closely examined the intestines of infected mice. pseudotuberculosis.

“We were interested in how the bacteria behaved in the gut, because this is an orally transmitted pathogen,” says Brodsky. “Daniel made the first observation that: Yersinia pseudotuberculosisInfections had previously undescribed macroscopic lesions along the length of the intestine. ”

A research team that included Solovethea and later a doctoral student in the lab, Rina Matsuda, confirmed that these same lesions were present when mice were infected. Y. enterocoliticaformed within 5 days after infection.

A biopsy of intestinal tissue confirmed that the lesions were a type of granuloma known as pyogenic granuloma, composed of various immune cells, including monocytes, neutrophils, bacteria and viruses.

Granulomas form in other diseases with chronic infections, such as tuberculosis. pseudotuberculosis is named. Somewhat paradoxically, these granulomas play an important role in controlling infection by lining the infecting agents, but maintaining a population of pathogens within their walls.

The team wanted to understand how these granulomas form and are maintained, so they used mice lacking monocytes and animals treated with monocyte-depleting antibodies. In animals that lack monocytes, “these granulomas have a unique structure and don’t form,” says Brodsky.

Instead, more deranged necrotic abscesses developed, neutrophils became less activated, and mice lost control over invading bacteria. succumbed to the infection.

Building a foundation for the future

Researchers believe that monocytes recruit neutrophils to sites of infection, initiate granuloma formation, and help control the bacteria. Researchers believe that this key role for monocytes may exist beyond the gut.

We hypothesize that there is also a general role for monocytes in other tissues. ”

Igor Brodsky, Senior Writer

However, these findings also indicate that the gut is an important site of involvement between the immune system and the body. Yersinia.

“Prior to this study, we knew that the Peyer’s patches are the main site of interaction of the body with the external environment through the mucosal tissue of the intestine,” Brodsky says. A small area of ​​lymphoid tissue that resides and plays a role in regulating the microbiome and preventing infection.

In future work, Brodsky and colleagues hope to continue to piece together the mechanism by which monocytes and neutrophils contain bacteria, a pursuit they pursued in collaboration with Sunny Shin’s lab in the Department of Microbiology at the Perelman School of Medicine. are doing.

A deeper understanding of the molecular pathways that regulate this immune response may one day enable forays into host-directed immunotherapy. Just trap them in the granuloma.

“These treatments have caused an explosion of excitement in the cancer field,” said Brodsky. infection too. ”