Endotoxin bacterial lipopolysaccharide (LPS)is a driver of lethal infection sepsis through excessive activation of innate immune responses. Researchers at Massachusetts General Hospital (MGH) have discovered a protein called NLRP11 that is crucial in alerting the body to bacterial infections and initiating an effective immune response to fight back against the invasion.
When human immune cells eat particular bacteria, NLRP11 recognizes them by recognizing a piece of their outer coat. This discovery could aid researchers in developing better “humanized” mouse models of infections and disorders involving the immune system.
The research focused on macrophages, immune cells that absorb and digest pathogens and increase the activity of other immune cells. A genetic screen found that macrophages require the NLRP11 gene to completely activate after consuming particular bacteria.
The gene’s NLRP11 protein allows a macrophage to detect the presence of bacterial lipopolysaccharide molecules within its core. When these compounds are detected, NLRP11 activates an inflammasome, an intracellular multimeric protein complex that promotes inflammatory responses to regulate infection.
This causes the caspase-4 enzyme, which is a component of the inflammasome, to be activated. These NLRP11 actions result in an effective immune system defense that kills invading bacterial cells and prevents widespread infection in the body.
Senior author Marcia B. Goldberg, MD, an investigator in the Division of Infectious Diseases at MGH and a professor in the Departments of Medicine and Microbiology at Harvard Medical School, said, “NLRP11 is present in humans and other primates but absent in mice, likely explaining why it has been missed previously, as most screens looking for innate immune signaling molecules have been carried out in mice.”
He added, “Our results demonstrate that NLRP11 is a previously missing link and a component of the human caspase-4 inflammasome activation pathway.”
The NLRP11 protein encoded by the gene allows macrophages to recognize the presence of bacterial lipopolysaccharide molecules within their core. NLRP11 triggers an inflammasome, an intracellular multimeric protein complex that promotes inflammatory responses to regulate infection when these substances are recognized.
This activates the caspase-4 enzymes, which is a component of the inflammasome. These NLRP11 actions result in an effective immune system defense that destroys invading bacterial cells and keeps the body from becoming infected.