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IgG in cervicovaginal mucus traps HSV and prevents vaginal Herpes infections
- Source :
- Mucosal immunology
- Publication Year :
- 2014
- Publisher :
- Elsevier BV, 2014.
-
Abstract
- IgG is the predominant immunoglobulin in cervicovaginal mucus (CVM), yet how immunoglobulin G (IgG) in mucus can protect against infections is not fully understood. IgG diffuses rapidly through cervical mucus, slowed only slightly by transient adhesive interactions with mucins. We hypothesize that this almost unhindered diffusion allows IgG to accumulate rapidly on pathogen surfaces, and the resulting IgG array forms multiple weak adhesive crosslinks to mucus gel that effectively trap (immobilize) pathogens, preventing them from initiating infections. Here, we report that herpes simplex virus serotype 1 (HSV-1) readily penetrated fresh, pH-neutralized ex vivo samples of CVM with low or no detectable levels of anti-HSV-1 IgG but was trapped in samples with even modest levels of anti-HSV-1 IgG. In samples with little or no endogenous anti-HSV-1 IgG, addition of exogenous anti-HSV-1 IgG, affinity-purified from intravenous immunoglobulin, trapped virions at concentrations below those needed for neutralization and with similar potency as endogenous IgG. Deglycosylating purified anti-HSV-1 IgG, or removing its Fc component, markedly reduced trapping potency. Finally, a non-neutralizing IgG against HSV-gG significantly protected mice against vaginal infection, and removing vaginal mucus by gentle lavage abolished protection. These observations suggest that IgG-Fc has a glycan-dependent "muco-trapping" effector function that may provide exceptionally potent protection at mucosal surfaces.
- Subjects :
- Adult
glycosylation
Herpesvirus 2, Human
Immunology
Herpesvirus 1, Human
medicine.disease_cause
Article
Vaginal mucus
Immunoglobulin G
Neutralization
particle tracking
Microbiology
Mice
Young Adult
03 medical and health sciences
0302 clinical medicine
antibody
Chlorocebus aethiops
medicine
Animals
Humans
Simplexvirus
Immunology and Allergy
Vero Cells
mucosa
030304 developmental biology
0303 health sciences
biology
diffusion
Mucin
Herpesviridae Infections
mucins
Mucus
3. Good health
Disease Models, Animal
Herpes simplex virus
030220 oncology & carcinogenesis
Vagina
Cervix Mucus
biology.protein
Female
Antibody
Ex vivo
Fluorescence Recovery After Photobleaching
Subjects
Details
- ISSN :
- 19330219
- Volume :
- 7
- Database :
- OpenAIRE
- Journal :
- Mucosal Immunology
- Accession number :
- edsair.doi.dedup.....d04fe09443cdd053c27164b39758a191