Differential Binding of IgG and IgA to Mucus of the Female Reproductive Tract

Cells of the endocervix are responsible for the secretion of mucins, which provide an additional layer of protection to the female reproductive tract (FRT). This barrier is likely fortified with IgA as has previously been shown in the gastrointestinal tract and lungs of mice. Mucus associated IgA can facilitate clearance of bacteria. While a similar function for IgG has been proposed, an association with mucus has not yet been demonstrated. Here we find that IgA and IgG are differentially associated with the different types of mucus of the FRT. We observed that while both IgA and IgG are stably associated with cervical mucus, only IgG is associated with cervicovaginal mucus. These findings reveal that antibodies can bind tightly to mucus, where they can play a significant role in the fortification of the mucus barriers of the FRT. It may be possible to harness this interaction in the development of vaccines designed to protect the FRT mucosal barriers from sexually transmitted diseases such as HIV.

[1]  I. Gipson,et al.  Mucin genes expressed by human female reproductive tract epithelia. , 1997, Biology of reproduction.

[2]  S Jager,et al.  The significance of the Fc part of antispermatozoal antibodies for the shaking phenomenon in the sperm-cervical mucus contact test. , 1981, Fertility and sterility.

[3]  V. Korolik,et al.  Mucins in the mucosal barrier to infection , 2008, Mucosal Immunology.

[4]  G. Preti,et al.  Vaginal odors and secretions. , 1981, Clinical obstetrics and gynecology.

[5]  C. Barros,et al.  Scanning electron microscope study of human cervical mucus , 1985 .

[6]  I. Gipson.  Mucins of the human endocervix. , 2001, Frontiers in bioscience : a journal and virtual library.

[7]  R. Bronson,et al.  The effect of an IgA1 protease on immunoglobulins bound to the sperm surface and sperm cervical mucus penetrating ability. , 1987, Fertility and sterility.

[8]  P. Hui,et al.  Expression of mucins, SIMA, villin, and CDX2 in small-intestinal adenocarcinoma. , 2007, American journal of clinical pathology.

[9]  P. Sansonetti,et al.  Secretory component: a new role in secretory IgA-mediated immune exclusion in vivo. , 2002, Immunity.

[10]  N. Kondo,et al.  Roles of anti-hemagglutinin IgA and IgG antibodies in different sites of the respiratory tract of vaccinated mice in preventing lethal influenza pneumonia. , 2003, Vaccine.

[11]  E. Chantler,et al.  THE SCANNING ELECTRONMICROSCOPY OF HUMAN CERVICAL MUCUS IN THE NON‐PREGNANT AND PREGNANT STATES , 1976, British journal of obstetrics and gynaecology.

[12]  J. Mestecky,et al.  Mucosal immunity in the female reproductive tract: correlation of immunoglobulins, cytokines, and reproductive hormones in human cervical mucus around the time of ovulation. , 1998, AIDS research and human retroviruses.

[13]  K. Whaley,et al.  Antibody diffusion in human cervical mucus. , 1994, Biophysical journal.

[14]  E. Linford.  Cervical mucus: an agent or a barrier to conception? , 1974, Journal of reproduction and fertility.

[15]  A. Biesbrock,et al.  Interaction of a salivary mucin-secretory immunoglobulin A complex with mucosal pathogens , 1991, Infection and immunity.

[16]  M. Johansson,et al.  Proteomic analyses of the two mucus layers of the colon barrier reveal that their main component, the Muc2 mucin, is strongly bound to the Fcgbp protein. , 2009, Journal of proteome research.

[17]  A. Janin,et al.  Mucin gene expression in the human endocervix. , 1995, Human reproduction.

[18]  J. Davies,et al.  MUC5AC, but not MUC2, is a prominent mucin in respiratory secretions , 1996, Glycoconjugate Journal.

[19]  R. Dwek,et al.  Secretory IgA N- and O-Glycans Provide a Link between the Innate and Adaptive Immune Systems* , 2003, Journal of Biological Chemistry.

[20]  G. Hansson,et al.  Large Scale Identification of Proteins, Mucins, and Their O-Glycosylation in the Endocervical Mucus during the Menstrual Cycle*S , 2007, Molecular & Cellular Proteomics.

[21]  D. Burr,et al.  Intestinal mucus gel and secretory antibody are barriers to Campylobacter jejuni adherence to INT 407 cells , 1987, Infection and immunity.

[22]  H. Ogata,et al.  Distribution and partial characterisation of IgG Fc binding protein in various mucin producing cells and body fluids , 2002, Gut.

[23]  P. Chu,et al.  Differential expression of MUC1, MUC2, and MUC5AC in carcinomas of various sites: an immunohistochemical study. , 2004, American journal of clinical pathology.

[24]  Miriam Cohen,et al.  Using Unfixed, Frozen Tissues to Study Natural Mucin Distribution , 2012, Journal of visualized experiments : JoVE.

[25]  A. Oshima,et al.  Human IgGFc Binding Protein (FcγBP) in Colonic Epithelial Cells Exhibits Mucin-like Structure* , 1997, The Journal of Biological Chemistry.

[26]  K. Magnusson,et al.  Mucosal barrier mechanisms. Interplay between secretory IgA (SIgA), IgG and mucins on the surface properties and association of salmonellae with intestine and granulocytes. , 1982, Immunology.