A new study that appeared in the journal Science Immunology has revealed a protein found in humans that play a crucial role in triggering effective protection against bacteria trying to invade the body.
Bacteria
The research revealed that the protein NLRP11 was the missing link for an effective fight against bacterial infection. This protein can be found in humans but is absent in mice, which are often used to study human conditions in laboratories.
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“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,” explained Marcia B. Goldberg, MD, senior study author and a researcher at MGH’s Division of Infectious Diseases.
This discovery may aid researchers in developing better “humanized” mouse models for studying infections and diseases in humans that involve the immune system.
The study was led by scientists from Massachusetts General Hospital (MGH).
The missing link
The focus of researchers in this study was on macrophages. These are immune cells that enclose and digest invading microorganisms and other harmful substances. They also help to bring other immune cells into action to fight harmful agents.
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Through a genetic screen, the research team found that the full activation of macrophages after engulfing certain bacteria depends on the NLRP11 gene. The protein that this gene produces makes it possible for a macrophage to detect bacterial lipopolysaccharide molecules inside it.
NLRP11 sets off an inflammasome. This is a multimeric protein complex of the innate immune system which switches on a pathway for the activation of inflammatory responses against infections. Specifically, NLRP11 helps to activate a part of this inflammasome – an enzyme called caspase-4.
Through its actions, the NLRP11 protein brings about a potent shield against invading bacteria. It helps to avert massive infection within the body.
“Our results demonstrate that NLRP11 is a previously missing link and a component of the human caspase-4 inflammasome activation pathway,” stated Goldberg, a professor in Harvard Medical School’s Departments of Medicine and Microbiology.
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The research team is exploring further the roles of NLRP11 in human macrophages. Goldberg and her colleagues are looking into the effects of the presence of the protein in humans compared to its absence in mice. They hope this would help to develop mouse macrophages that are more comparable to human ones to aid research into bacterial infections.
References
Rojas-Lopez, M., Gil-Marqués, M. L., Kharbanda, V., Zajac, A. S., … & Goldberg, M. B. (2023). NLRP11 is a pattern recognition receptor for bacterial lipopolysaccharide in the cytosol of human macrophages. Science Immunology, 8(85). https://doi.org/10.1126/sciimmunol.abo4767
