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Antibody-enhanced pneumococcal adherence requires IgA1 protease
Jeffrey N Weiser1, Deborah Bae, Claudine Fasching
1Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. weiser@mail.med.upenn.edu
Summary
Certain Streptococcus pneumoniae bacteria use IgA1 protease to enhance attachment to host cells. This enzyme may help pathogens evade immune responses and persist on mucosal surfaces.
Area of Science:
- Microbiology
- Immunology
- Pathogenesis
Background:
- Immunoglobulin A (IgA) is crucial for mucosal immunity, preventing pathogen adherence.
- Some bacteria, like Streptococcus pneumoniae, produce IgA1 protease to overcome IgA's protective effects.
Purpose of the Study:
- To investigate the role of human monoclonal antibodies (mAbs) against Streptococcus pneumoniae's capsular polysaccharide in bacterial adherence.
- To explore the novel function of bacterial IgA1 proteases in pathogen-host interactions.
Main Methods:
- Generated human mAbs against the pneumococcal capsular polysaccharide.
- Utilized a respiratory epithelial cell culture model to assess bacterial adherence.
- Analyzed the effect of IgA1 protease cleavage on antibody-mediated bacterial attachment.
Main Results:
- Type-specific IgA1, when cleaved by IgA1 protease, enhanced pneumococcal attachment to host cells.
- Antibodies of IgA2 and IgG subclasses, or those against different capsules, did not promote adherence.
- Cleaved antibody fragments (Fab) may neutralize negatively charged bacterial capsules, facilitating adherence.
- Antibody coating exposed bacterial phosphorylcholine, increasing adherence via the platelet-activating factor receptor.
Conclusions:
- Bacterial IgA1 proteases can subvert the immune response by facilitating pathogen adherence and persistence.
- Cleaved IgA1 antibodies can paradoxically enhance bacterial colonization rather than inhibit it.
- This study reveals a novel mechanism by which pathogens exploit host immune components for colonization.