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Updated: Jul 15, 2026
Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
Impaired host defense in mice lacking ONZIN
Julie G Ledford1, Martina Kovarova, Beverly H Koller
1Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, North Carolina 27599, USA.
Abstract:
ONZIN is a small, cysteine-rich peptide of unique structure that is conserved in all vertebrates examined to date. We show that ONZIN is expressed at high levels in epithelial cells of the intestinal tract, the lung, and in cells of the immune system including macrophages and granulocytes. Because this pattern of expression is suggestive of a role in innate immune function, we have generated mice lacking this protein and examined their ability to respond to challenge with infectious agents. Onzin(-/-) mice show a heightened innate immune response after induction of acute peritonitis with Klebsiella pneumoniae. This increased response is consistent with an increased bacterial burden in the Onzin(-/-) mice. Ex vivo studies show that, whereas phagocytosis is not altered in Onzin(-/-) neutrophils, phagocytes lacking this protein kill bacteria less effectively. This result identifies ONZIN as a novel class of intracellular protein required for optimal function of the neutrophils after uptake of bacteria.
Insights
ONZIN is a crucial protein for effective bacterial killing by neutrophils. Mice lacking ONZIN show impaired immune responses and higher bacterial loads, highlighting its role in innate immunity.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- ONZIN is a conserved, cysteine-rich peptide found in vertebrates.
- High expression in the intestinal tract, lung, and immune cells suggests a role in innate immunity.
Purpose of the Study:
- To investigate the function of ONZIN in the innate immune response.
- To determine the effect of ONZIN deficiency on host defense against bacterial infection.
Main Methods:
- Generation and analysis of Onzin knockout mice (Onzin(-/-)).
- Assessment of innate immune response to Klebsiella pneumoniae challenge.
- Ex vivo analysis of neutrophil function, including phagocytosis and bacterial killing.
Main Results:
- Onzin(-/-) mice exhibited a heightened innate immune response and increased bacterial burden after Klebsiella pneumoniae infection.
- Neutrophil phagocytosis was unaffected in Onzin(-/-) mice.
- Phagocytes lacking ONZIN demonstrated reduced bacterial killing capacity.
Conclusions:
- ONZIN is a novel intracellular protein essential for optimal neutrophil function after bacterial uptake.
- ONZIN plays a critical role in host defense against bacterial pathogens.
