BackgroundThe function of Toll-like receptor 2 (TLR2) in host defense against pathogens, especially Mycobacterium tuberculosis (Mtb) is poorly understood. To investigate the role of TLR2 during mycobacterial infection, we analyzed the response of tlr2 zebrafish mutant larvae to infection with Mycobacterium marinum (Mm), a close relative to Mtb, as a model for tuberculosis. We measured infection phenotypes and transcriptome responses using RNA deep sequencing in mutant and control larvae.Resultstlr2 mutant embryos at 2 dpf do not show differences in numbers of macrophages and neutrophils compared to control embryos. However, we found substantial changes in gene expression in these mutants, particularly in metabolic pathways, when compared with the heterozygote tlr2+/− control. At 4 days after Mm infection, the total bacterial burden and the presence of extracellular bacteria were higher in tlr2−/− larvae than in tlr2+/−, or tlr2+/+ larvae, whereas granuloma numbers were reduced, showing a function of Tlr2 in zebrafish host defense. RNAseq analysis of infected tlr2−/− versus tlr2+/− shows that the number of up-regulated and down-regulated genes in response to infection was greatly diminished in tlr2 mutants by at least 2 fold and 10 fold, respectively. Analysis of the transcriptome data and qPCR validation shows that Mm infection of tlr2 mutants leads to decreased mRNA levels of genes involved in inflammation and immune responses, including il1b, tnfb, cxcl11aa/ac, fosl1a, and cebpb. Furthermore, RNAseq analyses revealed that the expression of genes for Maf family transcription factors, vitamin D receptors, and Dicps proteins is altered in tlr2 mutants with or without infection. In addition, the data indicate a function of Tlr2 in the control of induction of cytokines and chemokines, such as the CXCR3-CXCL11 signaling axis.ConclusionThe transcriptome and infection burden analyses show a function of Tlr2 as a protective factor against mycobacteria. Transcriptome analysis revealed tlr2-specific pathways involved in Mm infection, which are related to responses to Mtb infection in human macrophages. Considering its dominant function in control of transcriptional processes that govern defense responses and metabolism, the TLR2 protein can be expected to be also of importance for other infectious diseases and interactions with the microbiome.

To explore the impact of chronic heat stress on commercial echinoderms, the present study assessed the effects of chronic high temperature on the growth, survival, feeding, and differential gene expression in the sea urchin Strongylocentrotus intermedius cultured in northern Yellow Sea in China. One suitable seawater condition (20°C) and one laboratory-controlled high temperature condition (25°C) were set up. After 28 days incubation, our results showed that: (1) The specific growth, survival, and ingestion rates of S. intermedius reared under high temperature (25°C) decreased compared to those reared under optimal temperature (20°C) conditions; (2) comparative transcriptome analysis identified 2,125 differentially expressed genes (DEGs) in S. intermedius reared under high temperature (25°C) compared to those subjected to optimal temperature condition (20°C), which included 1,015 upregulated and 1,100 downregulated genes. The accuracy of the transcriptome profiles was verified by quantitative real-time PCR (qRT-PCR). Further Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analyses revealed that these DEGs mainly enriched the functional categories of ribosome, protein processing in endoplasmic reticulum, and prion diseases. A total of 732 temperature-induced expressed genes, such as ATP5, heat shock protein 70, and heat shock protein 90, were identified as candidates that were closely correlated with heat resistance in S. intermedius . Differentially expressed transcription factors (TFs), such as AP-1, Fos, CREB, and ZNF, were also identified as potential regulators that regulate the molecular network that was associated with responses to heat stress in sea urchins. Observations in the present study provide additional information that improves our understanding of the molecular mechanism of temperate echinoid species in response to heat stress, as well as theoretical basis for the molecular-assisted breeding of heat-resistant sea urchins.

Innate immunity is considered the first line of defense against microbial invasion, and its dysregulation can increase the susceptibility of hosts to infections by invading pathogens. Host cells rely on pattern recognition receptors (PRRs) to recognize invading pathogens and initiate protective innate immune responses. Toll-like receptor 2 (TLR2) is believed to be among the most important Toll-like receptors for defense against mycobacterial infection. TLR2 has been reported to have very broad functions in infectious diseases and also in other diseases, such as chronic and acute inflammatory diseases, cancers, and even metabolic disorders. However, TLR2 has an unclear dual role in both the activation and suppression of innate immune responses. Moreover, in some studies, the function of TLR2 was shown to be controversial, and therefore its role in several diseases is still inconclusive. Therefore, although TLR2 has been shown to have an important function in innate immunity, its usefulness as a therapeutic target in clinical application is still uncertain. In this literature review, we summarize the knowledge of the functions of TLR2 in host–mycobacterial interactions, discuss controversial results, and suggest possibilities for future research.

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