Article

Serotonin and melatonin, neurohormones for homeostasis, as novel inhibitors of infections by the intracellular parasite Chlamydia

Yamaguchi University, Yamaguti, Yamaguchi, Japan
Journal of Antimicrobial Chemotherapy (Impact Factor: 5.31). 12/2005; 56(5):861-8. DOI: 10.1093/jac/dki331
Source: PubMed

ABSTRACT

Chlamydiae are obligate intracellular bacteria, causing a variety of diseases, i.e. pneumonia, sexually transmitted disease, conjunctivitis and zoonosis. Tryptophan depletion by interferon-gamma (IFN-gamma) is the most important host defence system against chlamydial infection. Thus chlamydial tryptophan metabolism is thought to play key roles for IFN-gamma resistance, persistent infection and host/tissue tropisms. We tested tryptophan derivatives for activity against chlamydia-infected cells.
Rates of chlamydial infection and sizes of the inclusions were evaluated by in vitro infection using three Chlamydiaceae species, Chlamydia trachomatis, Chlamydophila pneumoniae and Chlamydophila felis, which show significant divergence of tryptophan synthesis genes and different susceptibilities to IFN-gamma.
Melatonin and serotonin, which are recognized as neural hormones for maintenance of organism homeostasis, reduced chlamydial infection but not other bacterial growth tested here. Unlike IFN-gamma, melatonin limited infection of all three chlamydiae and the effects were not recovered by tryptophan supplementation. Melatonin treatment only of host cells could diminish infection and the infection reduction was neutralized by a pertussis toxin, an inhibitor of G proteins. Ligands of melatonin and serotonin receptors also hampered infection.
Inhibition mechanisms of chlamydial infection by melatonin and serotonin appear to be different from those of IFN-gamma and involve specific G-protein-coupled receptors. Melatonin is deemed to inhibit early progression of the chlamydial development cycle, such as establishment of intracellular infection and/or conversion from elementary body to reticulate body. Utilization of melatonin, serotonin or their derivatives may be advantageous for harmless prevention of chlamydial infection.

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    • "cells, suppressed formation of the intercellular matrix, and inhibited the growth of the aforementioned bacteria (Oleskin et al., 1998 ). Interestingly, serotonin suppressed the development of intracellular chlamydia (Rahman et al., 2005) and attenuated the virulence of Candida albicans (Mayr et al., 2005). The stimulatory effect of serotonin on pro-and eukaryotic cells can be hypothetically attributed to the presence of receptors to serotonin and, presumably, to related compounds (e.g., indole) in them. "

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    • "Melatonin is pleiotropic and affects multiple systems with remarkable functional versatility, including immunostimulatory (Guerrero and Reiter, 2002; Carrillo-Vico et al., 2005), anti-inflammatory (Jung et al., 2010; Szczepanik, 2007; Chahbouni et al., 2010), and antioxidant (Galano et al., 2011; Suzen, 2013) roles. In addition, melatonin protects the host from pathogens, such as retroviruses (Zhang et al., 1999), Chlamydia (Rahman et al., 2005), Plasmodium (Hotta et al., 2003) and T. cruzi (Oliveira et al., 2010). The anti-inflammatory properties of melatonin can be explained by its effect on NF-␬␤ because this transcription factor regulates numerous genes involved in the immune response and inflammation . "
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