CLec-TM1-ERK-GSK3ß Pathway Regulates Vibrio splendidus-Induced IL-17 Production in Oyster.

C-type lectins are a family of pattern recognition receptors that recognize microbial components and subsequently activate the signaling cascade to induce the production of proinflammatory cytokines. In the current study, the homologs of ERK (named as CgERK) and GSK3ß (named as CgGSK3ß) and a novel C-type lectin with a transmembrane domain (named as CgCLec-TM1) were identified from oyster Crassostrea gigas CgCLec-TM1 was able to bind Escherichia coli and Vibrio splendidus through its carbohydrate recognition domain and then activated CgERK by inducing its phosphorylation. The activated CgERK interacted with CgGSK3ß to phosphorylate it at Ser9, which eventually induced the expressions of CgIL-17-1 and CgIL-17-5. The interaction between CgERK and CgGSK3ß, as well as the phosphorylation of CgGSK3ß, could be inhibited by ERK inhibitor (PD98059) to reduce the expressions of CgIL-17-1 and CgIL-17-5. CgGSK3ß in oyster was proposed as a new substrate of CgERK. The results defined a CLec-TM1-ERK-GSK3ß signaling pathway in oyster, which was activated by V. splendidus and then induced CgIL-17 productions.

A novel C-type lectin activates the complement cascade in the primitive oyster Crassostrea gigas.

The ancient origin of the lectin pathway of the complement system can be traced back to protochordates (such as amphioxus and tunicates) by the presence of components such as ficolin, glucose-binding lectin, mannose-binding lectin-associated serine protease (MASP), and C3. Evidence for a more primitive origin is offered in the present study on the Pacific oyster Crassostrea gigas. C3 protein in C. gigas (CgC3) was found to be cleaved after stimulation with the bacteria Vibrio splendidus. In addition, we identified a novel C-type lectin (defined as CgCLec) with a complement control protein (CCP) domain, which recognized various pathogen-associated molecular patterns (PAMPs) and bacteria. This protein was involved in the activation of the complement system by binding CgMASPL-1 to promote cleavage of CgC3. The production of cytokines and antibacterial peptides, as well as the phagocytotic ratio of haemocytes in CgCLec-CCP-, CgMASPL-1-, or CgC3-knockdown oysters, decreased significantly after V. splendidus stimulation. Moreover, this activated CgC3 participated in perforation of bacterial envelopes and inhibiting survival of the infecting bacteria. These results collectively suggest that there existed an ancient lectin pathway in molluscs, which was activated by a complement cascade to regulate the production of immune effectors, phagocytosis, and bacterial lysis.

Concurrent Hearing and Genetic Screening of 180,469 Neonates with Follow-up in Beijing, China.

Concurrent hearing and genetic screening of newborns is expected to play important roles not only in early detection and diagnosis of congenital deafness, which triggers intervention, but also in predicting late-onset and progressive hearing loss and identifying individuals who are at risk of drug-induced HL. Concurrent hearing and genetic screening in the whole newborn population in Beijing was launched in January 2012. This study included 180,469 infants born in Beijing between April 2013 and March 2014, with last follow-up on February 24, 2018. Hearing screening was performed using transiently evoked otoacoustic emission (TEOAE) and automated auditory brainstem response (AABR). For genetic testing, dried blood spots were collected and nine variants in four genes, GJB2, SLC26A4, mtDNA 12S rRNA, and GJB3, were screened using a DNA microarray platform. Of the 180,469 infants, 1,915 (1.061%) were referred bilaterally or unilaterally for hearing screening; 8,136 (4.508%) were positive for genetic screening (heterozygote, homozygote, or compound heterozygote and mtDNA homoplasmy or heteroplasmy), among whom 7,896 (4.375%) passed hearing screening. Forty (0.022%) infants carried two variants in GJB2 or SLC26A4 (homozygote or compound heterozygote) and 10 of those infants passed newborn hearing screening. In total, 409 (0.227%) infants carried the mtDNA 12S rRNA variant (m.1555A>G or m.1494C>T), and 405 of them passed newborn hearing screening. In this cohort study, 25% of infants with pathogenic combinations of GJB2 or SLC26A4 variants and 99% of infants with an m.1555A>G or m.1494C>T variant passed routine newborn hearing screening, indicating that concurrent screening provides a more comprehensive approach for management of congenital deafness and prevention of ototoxicity.