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Ehrlichia chaffeensis Outer Membrane Protein 1-Specific Human Antibody-Mediated Immunity Is Defined by Intracellular TRIM21-Dependent Innate Immune Activation and Extracellular Neutralization
- Source :
- Infection and Immunity
- Publication Year :
- 2019
- Publisher :
- American Society for Microbiology, 2019.
-
Abstract
- Antibodies are essential for immunity against Ehrlichia chaffeensis, and protective mechanisms involve blocking of ehrlichial attachment or complement and Fcγ-receptor-dependent destruction. In this study, we determined that major outer membrane protein 1 (OMP-19) hypervariable region 1 (HVR1)-specific human monoclonal antibodies (huMAbs) are protective through conventional extracellular neutralization and, more significantly, through a novel intracellular TRIM21-mediated mechanism.<br />Antibodies are essential for immunity against Ehrlichia chaffeensis, and protective mechanisms involve blocking of ehrlichial attachment or complement and Fcγ-receptor-dependent destruction. In this study, we determined that major outer membrane protein 1 (OMP-19) hypervariable region 1 (HVR1)-specific human monoclonal antibodies (huMAbs) are protective through conventional extracellular neutralization and, more significantly, through a novel intracellular TRIM21-mediated mechanism. Addition of OMP-1-specific huMAb EHRL-15 (IgG1) prevented infection by blocking attachment/entry, a mechanism previously reported; conversely, OMP-1-specific huMAb EHRL-4 (IgG3) engaged intracellular TRIM21 and initiated an immediate innate immune response and rapid intracellular degradation of ehrlichiae. EHRL-4-TRIM21-mediated inhibition was significantly impaired in TRIM21 knockout THP-1 cells. EHRL-4 interacted with cytosolic Fc receptor TRIM21, observed by confocal microscopy and confirmed by co-immunoprecipitation. E. chaffeensis-EHRL-4-TRIM21 complexes caused significant upregulation of proinflammatory cytokine/chemokine transcripts and resulted in rapid (
- Subjects :
- Chemokine
THP-1 Cells
Immunology
Fc receptor
Microbiology
Bacterial Adhesion
Gene Knockout Techniques
Cell Line, Tumor
Autophagy
Extracellular
Humans
Ehrlichia chaffeensis
neutralizing antibodies
Spotlight
selective autophagy
Antigens, Bacterial
Innate immune system
LAMP2
biology
Adenine
NF-kappa B
Antibodies, Monoclonal
biology.organism_classification
Antibodies, Neutralizing
Immunity, Humoral
Cell biology
Infectious Diseases
Ribonucleoproteins
human monoclonal antibodies
Microbial Immunity and Vaccines
biology.protein
bacteria
Parasitology
CRISPR-Cas Systems
antibody function
TRIM21
Intracellular
Bacterial Outer Membrane Proteins
Subjects
Details
- ISSN :
- 10985522 and 00199567
- Volume :
- 87
- Database :
- OpenAIRE
- Journal :
- Infection and Immunity
- Accession number :
- edsair.doi.dedup.....89c60edfe1186c65f0dd7d7d0716ba94
- Full Text :
- https://doi.org/10.1128/iai.00383-19