Illustration of lungs intertwined with a protein network, symbolizing β5i/LMP7 deficiency.

Can a Protein Complex Deficiency Worsen Pneumonia?

Nico Varela in Health & Wellness November 2025 • 4 min read.

"New research reveals how a missing link in your immune system could make you more susceptible to severe pneumonia."

Pneumonia, an infection that inflames the air sacs in one or both lungs, is a serious health concern, especially when it leads to complications or severe illness. The body relies on a complex interplay of immune responses to combat such infections, and scientists are continually working to understand these mechanisms fully.

The ubiquitin proteasome system (UPS) is critical for regulating various cellular processes, including the immune response. Within the UPS, immunoproteasomes play a crucial role in modifying immune responses during infections. These specialized proteasomes, containing subunits like β5i/LMP7, help fine-tune the body's defense mechanisms.

New research has uncovered a surprising link between a deficiency in the β5i/LMP7 immunoproteasome subunit and the severity of pneumococcal pneumonia. This article explores how this deficiency affects the body's ability to fight off the infection and what it could mean for future treatments.

How β5i/LMP7 Deficiency Aggravates Pneumonia

Illustration of lungs intertwined with a protein network, symbolizing β5i/LMP7 deficiency.

Researchers investigated the impact of β5i/LMP7 deficiency on the course of Streptococcus pneumoniae infection, a common cause of pneumonia. They observed that mice lacking this subunit experienced more severe clinical signs, including a greater loss of body weight and a more pronounced expression of serum amyloid A (SAA), an indicator of acute inflammation.

The study revealed that β5i/LMP7-deficient mice had a higher mortality rate during the early stages of infection. Further analysis showed these mice developed sepsis, a life-threatening condition caused by an overwhelming immune response, with a significant decrease in circulating leukocytes (immune cells) compared to healthy mice.

Granulocyte Recruitment: The recruitment of granulocytes, a type of white blood cell, was diminished in β5i/LMP7-deficient mice, indicating a compromised immune response.
Leukopenia and Lymphopenia: A significant decrease in leukocytes, particularly lymphocytes, was observed in the deficient mice, suggesting a systemic immune suppression.
Elevated LDH Levels: Increased levels of lactate dehydrogenase (LDH), an enzyme released upon tissue damage, were found in the serum of β5i/LMP7-deficient mice, indicating greater tissue injury.

Bacterial dissemination was also aggravated in the deficient mice, with a significantly higher bacterial load in the blood compared to wild-type animals. This indicates that the β5i/LMP7 subunit plays a crucial role in controlling the spread of infection.

What This Means for You

The study suggests that the β5i/LMP7 subunit is vital for modulating the innate immune response to extracellular bacterial infections like Streptococcus pneumoniae. A deficiency in this subunit can lead to reduced opsonin expression, impairing the body's ability to recognize and eliminate bacteria effectively.

While this research is still in its early stages, it highlights the potential importance of immunoproteasomes in maintaining a robust immune system. Further studies are needed to determine whether these findings can be translated into new treatments or preventive strategies for pneumonia.

Understanding the role of immunoproteasomes in immune defense may pave the way for novel therapeutic interventions targeting the UPS, ultimately improving outcomes for individuals at risk of severe pneumonia.

About this Article -

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This article is based on research published under:

DOI-LINK: 10.1371/journal.pone.0153847, Alternate LINK

Title: Proteasome Β5I Subunit Deficiency Affects Opsonin Synthesis And Aggravates Pneumococcal Pneumonia

Subject: Multidisciplinary

Journal: PLOS ONE

Publisher: Public Library of Science (PLoS)

Authors: Felicia Kirschner, Katrin Reppe, Nadine Andresen, Martin Witzenrath, Frédéric Ebstein, Peter-Michael Kloetzel

Published: 2016-04-21

Everything You Need To Know

How does a deficiency in the β5i/LMP7 immunoproteasome subunit affect someone with pneumococcal pneumonia?

A deficiency in the β5i/LMP7 immunoproteasome subunit can worsen pneumococcal pneumonia. Research indicates that individuals lacking this subunit may experience more severe clinical signs, such as greater weight loss, increased acute inflammation (indicated by serum amyloid A or SAA), a higher mortality rate, and a greater susceptibility to sepsis. Furthermore, it can lead to decreased circulating leukocytes, impairing the body's ability to effectively fight off the infection. This deficiency impairs opsonin expression, which is crucial for the recognition and elimination of bacteria. Related topics not covered in this study, but relevant, could include the long-term impacts of β5i/LMP7 deficiency on pneumonia recovery and potential therapeutic interventions.

What is the role of the ubiquitin proteasome system (UPS) in fighting infections like pneumonia?

The ubiquitin proteasome system (UPS) is vital for regulating cellular processes, including the immune response, which is crucial for fighting infections like pneumonia. Within the UPS, immunoproteasomes, such as those containing the β5i/LMP7 subunit, modify immune responses during infections, fine-tuning the body's defense mechanisms. While the article highlights the role of β5i/LMP7, it does not cover the broader mechanisms of antigen processing and presentation facilitated by the UPS, which are essential for adaptive immunity.

What is serum amyloid A (SAA), and what does its expression indicate in the context of pneumonia?

Serum amyloid A (SAA) is a protein whose expression is an indicator of acute inflammation. In the context of pneumonia, a more pronounced expression of SAA suggests a greater inflammatory response in the body, which can be indicative of a more severe infection. In β5i/LMP7-deficient mice, increased SAA levels correlated with the severity of their condition during Streptococcus pneumoniae infection. While the text mentions SAA as an indicator of inflammation, it does not detail the specific pathways that lead to its increased production or its direct effects on pneumonia pathogenesis.

Why did the β5i/LMP7-deficient mice experience a higher bacterial load in their blood during the Streptococcus pneumoniae infection?

The β5i/LMP7-deficient mice experienced a higher bacterial load in their blood because the deficiency impaired their ability to control the spread of infection. The β5i/LMP7 subunit plays a crucial role in modulating the innate immune response to bacterial infections like Streptococcus pneumoniae. A deficiency in this subunit can reduce opsonin expression, impairing the body's ability to recognize and eliminate bacteria effectively, leading to increased bacterial dissemination. The text doesn't fully elaborate on the specific mechanisms by which β5i/LMP7 influences opsonin expression and bacterial clearance, which involves complex interactions with other immune cells and molecules.

What are granulocytes, and why is their recruitment diminished in β5i/LMP7-deficient mice with pneumonia?

Granulocytes are a type of white blood cell essential for the immune response against infections. In β5i/LMP7-deficient mice with pneumonia, the recruitment of granulocytes was diminished, indicating a compromised immune response. This reduced recruitment impairs the body's ability to effectively combat the bacterial infection, as granulocytes play a key role in phagocytosis and inflammation. While this diminished recruitment of granulocytes was observed, the underlying molecular mechanisms or specific signaling pathways affected by β5i/LMP7 deficiency that lead to this outcome are not discussed.