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Myeloid-related protein-8/14 facilitates bacterial growth during pneumococcal pneumonia
Ahmed Achouiti1, Thomas Vogl2, Henrik Endeman3
1Center for Experimental and Molecular Medicine, University of Amsterdam, Amsterdam, The Netherlands Center for Infection and Immunity, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Background:
Streptococcus pneumoniae is the most commonly identified pathogen in community-acquired pneumonia (CAP). Myeloid-related protein (MRP) 8/14 is a major component of neutrophils that is released upon infection or injury. MRP8/14 is essential for protective immunity during infection by a variety of micro-organisms through its capacity to chelate manganese and zinc. Here, we aimed to determine the role of MRP8/14 in pneumococcal pneumonia.
Methods:
MRP8/14 was determined in bronchoalveolar lavage fluid (BALF) and serum of CAP patients, in lung tissue of patients who had succumbed to pneumococcal pneumonia, and in BALF of healthy subjects challenged with lipoteichoic acid (a component of the gram-positive bacterial cell wall) via the airways. Pneumonia was induced in MRP14 deficient and normal wildtype mice. The effect of MRP8/14 on S. pneumoniae growth was studied in vitro.
Results:
CAP patients displayed high MRP8/14 levels in BALF, lung tissue and serum. Healthy subjects challenged with lipoteichoic acid demonstrated elevated MRP8/14 in BALF. Likewise, mice with pneumococcal pneumonia had high MRP8/14 levels in lungs and the circulation. MRP14 deficiency, however, was associated with reduced bacterial growth and lethality, in the absence of notable effects on the inflammatory response. High zinc levels strongly inhibited growth of S. pneumoniae in vitro, which was partially reversed by MRP8/14.
Conclusions:
In sharp contrast to its previously reported host-protective role in several infections, the present results reveal that in a model of CAP, MRP8/14 is misused by S. pneumoniae, facilitating bacterial growth by attenuating zinc toxicity toward the pathogen.
Insights
Myeloid-related protein (MRP) 8/14 aids Streptococcus pneumoniae growth in pneumonia by reducing zinc toxicity. This contrasts with its known protective role in other infections, highlighting a pathogen-specific manipulation.
Area of Science:
- Infectious Diseases
- Immunology
- Microbiology
Background:
- Streptococcus pneumoniae is a primary cause of community-acquired pneumonia (CAP).
- Myeloid-related protein (MRP) 8/14, a neutrophil component, typically aids immunity by chelating zinc and manganese.
- The role of MRP8/14 in pneumococcal pneumonia was previously unclear.
Purpose of the Study:
- To investigate the specific role of MRP8/14 in the context of pneumococcal pneumonia.
- To understand how MRP8/14 influences the host's response to Streptococcus pneumoniae infection.
Main Methods:
- MRP8/14 levels were measured in patient samples (BALF, serum, lung tissue) and in healthy subjects exposed to lipoteichoic acid.
- Pneumonia was induced in mice lacking MRP14 and in wildtype mice.
- The in vitro effect of MRP8/14 on S. pneumoniae growth was assessed.
Main Results:
- Elevated MRP8/14 levels were observed in CAP patients and in mice with pneumococcal pneumonia.
- MRP14-deficient mice showed reduced bacterial growth and lethality.
- In vitro, high zinc levels inhibited S. pneumoniae growth, an effect partially reversed by MRP8/14.
Conclusions:
- Contrary to its known protective functions, MRP8/14 facilitates S. pneumoniae growth in pneumonia.
- Streptococcus pneumoniae appears to exploit MRP8/14 to overcome zinc-mediated growth inhibition.
- This study reveals a novel mechanism of pathogen manipulation in community-acquired pneumonia.
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