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A teleost CD46 is involved in the regulation of complement activation and pathogen infection.

ABSTRACT: In mammals, CD46 is involved in the inactivation of complement by factor I (FI). In teleost, study on the function of CD46 is very limited. In this study, we examined the immunological property of a CD46 molecule (CsCD46) from tongue sole, a teleost species with important economic value. We found that recombinant CsCD46 (rCsCD46) interacted with FI and inhibited complement activation in an FI-dependent manner. rCsCD46 also interacted with bacterial pathogens via a different mechanism to that responsible for the FI interaction, involving different rCsCD46 sites. Cellular study showed that CsCD46 was expressed on peripheral blood leukocytes (PBL) and protected the cells against the killing effect of complement. When the CsCD46 on PBL was blocked by antibody before incubation of the cells with bacterial pathogens, cellular infection was significantly reduced. Consistently, when tongue sole were infected with bacterial pathogens in the presence of rCsCD46, tissue dissemination and survival of the pathogens were significantly inhibited. These results provide the first evidence to indicate that CD46 in teleosts negatively regulates complement activation via FI and protects host cells from complement-induced damage, and that CD46 is required for optimal bacterial infection probably by serving as a receptor for the bacteria.

SUBMITTER: Li MF

PROVIDER: S-EPMC5670209 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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A teleost CD46 is involved in the regulation of complement activation and pathogen infection.

Li Mo-Fei MF Sui Zhi-Hai ZH Sun Li L

Scientific reports 20171103 1

In mammals, CD46 is involved in the inactivation of complement by factor I (FI). In teleost, study on the function of CD46 is very limited. In this study, we examined the immunological property of a CD46 molecule (CsCD46) from tongue sole, a teleost species with important economic value. We found that recombinant CsCD46 (rCsCD46) interacted with FI and inhibited complement activation in an FI-dependent manner. rCsCD46 also interacted with bacterial pathogens via a different mechanism to that res ...[more]

PMID: 29101395

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Project description:Viruses are able to interfere with the immune system by docking to receptors on host cells that are important for proper functioning of the immune system. A well-known example is the human immunodeficiency virus that uses CD4 cell surface molecules to enter host lymphocytes and thereby deleteriously destroying the helper cell population of the immune system. A more complicated mechanism is seen in multiple sclerosis (MS) where human herpes virus-6A (HHV-6A) infects astrocytes by docking to the CD46 surface receptor. Such HHV-6A infection in the brain of MS patients has recently been postulated to enable Epstein-Barr virus (EBV) to transform latently infected B-lymphocytes in brain lesions leading to the well-known phenomenon of oligoclonal immunoglobulin production that is widely used in the diagnosis of MS. The cellular immune response to HHV-6A and EBV is one part of the pathogenic mechanisms in MS. A more subtle pathogenic mechanism can be seen in the downregulation of CD46 on astrocytes by the infecting HHV-6A. Since CD46 is central in regulating the complement system, a lack of CD46 can lead to hyperactivation of the complement system. In fact, activation of the complement system in brain lesions is a well-known pathogenic mechanism in MS. In this review, it is postulated that a similar mechanism is central in the development of age-related macular degeneration (AMD). One of the earliest changes in the retina of AMD patients is the loss of CD46 expression in the retinal pigment epithelial (RPE) cells in the course of geographic atrophy. Furthermore, CD46 deficient mice spontaneously develop dry-type AMD-like changes in their retina. It is also well known that certain genetic polymorphisms in the complement-inhibiting pathways correlate with higher risks of AMD development. The tenet is that HHV-6A infection of the retina leads to downregulation of CD46 and consequently to hyperactivation of the complement system in the eyes of susceptible individuals.

Dataset Information

A teleost CD46 is involved in the regulation of complement activation and pathogen infection.

Publications

A teleost CD46 is involved in the regulation of complement activation and pathogen infection.

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