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Galectins as potential therapeutic targets in STIs in the female genital tract

Nature Reviews Urology volume 19, pages 240–252 (2022)Cite this article

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Abstract

Every day, more than one million people worldwide acquire a sexually transmitted infection (STI). This public health problem has a direct effect on women’s reproductive and sexual health as STIs can cause irreversible damage to fertility and can have negative consequences associated with discrimination and social exclusion. Infection with one sexually transmitted pathogen predisposes to co-infection with others, suggesting the existence of shared pathways that serve as molecular links between these diseases. Galectins, a family of β-galactoside-binding proteins, have emerged as endogenous mediators that facilitate cell-surface binding, internalization and cell invasion of many sexually transmitted pathogens, including Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, Candida albicans, HIV and herpes simplex virus. The ability of certain galectins to dimerize or form multimeric complexes confers the capacity to interact simultaneously with glycosylated ligands on both the pathogen and the cervico-vaginal tissue on these proteins. Galectins can act as a bridge by engaging glycans from the pathogen surface and glycosylated receptors from host cells, which is a mechanism that has been shown to be shared by several sexually transmitted pathogens. In the case of viruses and obligate intracellular bacteria, binding to the cell surface promotes pathogen internalization and cell invasion. Inflammatory responses that occur in cervico-vaginal tissue might trigger secretion of galectins, which in turn control the establishment, evolution and severity of STIs. Thus, galectin-targeted therapies could potentially prevent or decrease STIs caused by a diverse array of pathogenic microorganisms; furthermore, anti-galectin agents might reduce treatment costs of STIs and reach the most vulnerable populations.

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Fig. 1: Anatomical and histological structure of the female genital tract, different epithelia and associated microbiota.
Fig. 2: Role of galectins in host–pathogen interactions in sexually transmitted infections in the female genital tract.
Fig. 3: Alterations of the female genital tract might promote the development of sexually transmitted infections via galectin-dependent mechanisms.

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Acknowledgements

Work in M.T.D.’s and G.A.R.’s labs is supported by grants from the Agency for Promotion of Science and Technology (PICT 2016-1851 and PICT 2018-03737 to M.T.D. and PICT 2017-0494 to G.A.R.) as well as grants from SIIP-UNCUYO 2019 to M.T.D. and NIH grant CA221208 to G.A.R. and D.O.C. The authors are also thankful for generous support from Sales, Bunge & Born and Richard Lounsbery Foundations to G.A.R.

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Author notes

  1. Agustin L. Lujan

    Present address: Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain

  2. These authors jointly supervised this work: Gabriel A. Rabinovich, Maria T. Damiani.

Authors and Affiliations

  1. Laboratorio de Bioquímica e Inmunidad, Instituto de Bioquímica y Biotecnología, Facultad de Ciencias Médicas, Instituto de Medicina y Biología Experimental de Cuyo (IMBECU), Universidad Nacional de Cuyo (UNCUYO), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Mendoza, Argentina

    Agustin L. Lujan & Maria T. Damiani

  2. Laboratorio de Inmunopatología, Facultad de Ciencias Exactas y Naturales, Instituto de Histología y Embriología de Mendoza (IHEM), Universidad Nacional de Cuyo (UNCUYO), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Mendoza, Argentina

    Diego O. Croci

  3. Laboratorio de Glicomedicina, Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina

    Gabriel A. Rabinovich

  4. Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires (UBA), C1428AGE, Buenos Aires, Argentina

    Gabriel A. Rabinovich

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All authors researched data for the article, made substantial contributions to discussions of content, wrote the manuscript and reviewed and edited the manuscript before submission.

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Lujan, A.L., Croci, D.O., Rabinovich, G.A. et al. Galectins as potential therapeutic targets in STIs in the female genital tract. Nat Rev Urol 19, 240–252 (2022). https://doi.org/10.1038/s41585-021-00562-1

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