# IL-6–Caspase 3 Axis Plays an Important Role in Enteritis Caused by Legionella pneumophila Pulmonary Infection

## TL;DR

This study reveals how a strong-virulence strain of Legionella pneumophila causes enteritis through an IL-6–caspase 3 pathway during pulmonary infection.

## Contribution

The study identifies the IL-6–caspase 3 axis as a novel mechanism linking pulmonary infection to intestinal inflammation.

## Key findings

- Systemic inflammation is crucial for the enteritis caused by a strong-virulence Lp strain.
- IL-6 downregulates Bcl-2 via the p53 pathway, activating caspase 3 in intestinal cells.
- Caspase 3 activation leads to intestinal epithelial cell apoptosis and enteritis.

## Abstract

Background: Since Legionella pneumophila (Lp) is widely present in natural and artificial water environments, it has a high potential risk of outbreak. Diarrhea caused by Lp pulmonary infection is an important symptom of Legionnaires’ disease (LD); however, the underlying mechanism of the diarrhea has not yet been revealed. This not only has a negative impact on clinical diagnosis and treatment, but may also cause misdiagnosis. Methods: In the present study, a mouse model of enteritis caused by pulmonary infection of Lp was established. By using this mouse model, we explored the underlying mechanisms of the enteritis caused by Lp pulmonary infection. Results: The results indicated that the systemic inflammatory response played a very important role in the enteritis phenotype caused by a strong-virulence strain of Lp. Furthermore, we found that the expression of Bcl-2 was downregulated by IL-6 through the p53 signaling pathway, thereby activating the caspase 3 of intestinal epithelial cells (IECs), causing the apoptosis of IECs, and ultimately leading to the enteritis phenotype. Conclusions: The IL-6–caspase 3 axis plays an important role in enteritis caused by Lp pulmonary infection.