Search

Background: Defensins comprise a large family of cationic antimicrobial peptides that are characterized by the presence of a conserved cysteine-rich defensin motif. Based on the spacing pattern of cysteines, these defensins are broadly divided into five groups, namely plant, invertebrate, α-, β-, and θ-defensins, with the last three groups being mostly found in mammalian species. However, the evolutionary relationships among these five groups of defensins remain controversial. Results: Following a comprehensive screen, here we report that the chicken genome encodes a total of 13 different β-defensins but with no other groups of defensins being discovered. These chicken β-defensin genes, designated as Gallinacin 1-13, are clustered densely within a 86-Kb distance on the chromosome 3q3.5-q3.7. The deduced peptides vary from 63 to 104 amino acid residues in length sharing the characteristic defensin motif. Based on the tissue expression pattern, 13 β-defensin genes can be divided into two subgroups with Gallinacin 1-7 being predominantly expressed in bone marrow and the respiratory tract and the remaining genes being restricted to liver and the urogenital tract. Comparative analysis of the defensin clusters among chicken, mouse, and human suggested that vertebrate defensins have evolved from a single β-defensin-like gene, which has undergone rapid duplication, diversification, and translocation in various vertebrate lineages during evolution. Conclusions: We conclude that the chicken genome encodes only β-defensin sequences and that all mammalian defensins are evolved from a common β-defensin-like ancestor. The α-defensins arose from θ-defensins by gene duplication, which may have occurred after the divergence of mammals from other vertebrates, and θ-defensins have arisen from α-defensins specific to the primate lineage. Further analysis of these defensins in different vertebrate lineages will shed light on the mechanisms of host defense and evolution of innate immunity. [ABSTRACT FROM AUTHOR]

Septic shock, caused by exaggerated host responses to various microbial products typified by lipopolysaccharide (LPS), remains the leading cause of death in trauma patients. Gaining insight into the nature of host interactions with LPS will certainly facilitate attempts to develop effective anti-sepsis drugs. Tremendous progress has been made during the past few years in understanding the mechanisms of pathogen-induced host responses. Toll-like receptor (TLR) 4 and 2 have been implicated as major receptors for signaling initiated by LPS and many other microbial products following their binding to CD14. In addition, many signaling intermediates involved in LPSinduced cell activation, particularly activation of the transcription factor NF-κB, have been identified and characterized. Further investigations with these molecules will certainly reward us with more effective therapeutic drugs to treat septic shock as well as many other inflammatory and infectious disorders. [ABSTRACT FROM PUBLISHER]

Aphis gossypii Glover is a polyphagous herbivore that causes serious damage to cottons. Current understanding to trap its population is limited in the field approach. In this study, a two-year-course study was conducted to test the yellow sticky card (YSC) effects of orientation (east, up, west, and bottom) and height (30, 60, and 90 cm over the cotton crown) on numbers of trapped A. gossypii every three days in ninth days after explosion in a cotton plantation in Shihezi, Xinjiang, Northwest China in 2014 and 2015. In 2014, YSCs in the east orientation at a height of 60 cm trapped the highest number of A. gossypii five days after explosion. In 2015, highest number of A. gossypii were trapped by YSCs in the up orientation at a height of 30 cm. Our results showed that YSC in the up orientation at 30-60 cm over the cotton crown can trap the highest number of A. gossypii since the five to seven days after aphid explosion. In conclusion, the spatial placement of sticky cards can be available to trap the maximum number of pests which should be incorporated into observations in continuous years. [ABSTRACT FROM AUTHOR]

Immune checkpoint blockade (ICB) is a powerful oncologic treatment modality for a wide variety of human malignancies, but the patient response rate to this treatment remains low, especially in patients with cutaneous squamous cell carcinoma (cSCC). 5-Aminoleuvulinic acid-photodynamic therapy (ALAPDT) is widely used to treat cancerous and precancerous skin diseases, but the value of ALA-PDT in the treatment of invasive cSCC is debatable. Our previous studies have shown that ALA-PDT can induce antitumor immune responses by promoting the immunogenic death of tumor cells. However, it is unclear whether ALA-PDT exerts synergistic effects with ICB in cSCC. Here, we report that PD-L1 blockade potentiates the antitumor effects of ALA-PDT both on primary and distant tumors, and optimizes the tumor microenvironment in cSCC. In this study, we first detected PD-L1 expression in patients with different grades of cSCC. Then we found the combination of anti-PD-L1 monoclonal antibody (mAb) and ALA-PDT killed tumor cells by apoptosis- and/or ferroptosis-mediated immunogenic cell death (ICD) and stimulated systemic immune response, as well as building the immunological memory response to prevent tumor recurrence. Furthermore, we found that combination therapy can be used to recruit tertiary lymphoid structure (TLS)-like intratumoral lymphoid aggregates, which may promote tumorinfiltrating lymphocyte (TIL)-mediated antitumor immunity. In summary, our work demonstrates that ICB treatment with an anti-PD-L1 antibody is a promising strategy that may potentiate the antitumor effects of ALA-PDT in cSCC. [ABSTRACT FROM AUTHOR]

The gastrointestinal (GI) tract harbors a diverse population of microorganisms. While much work has been focused on the characterization of the bacterial community, very little is known about the fungal community, or mycobiota, in different animal species and chickens in particular. Here we characterized the biogeography of the mycobiota along the GI tract of day-28 broiler chicks and further examined its possible shift in response to bacitracin methylene disalicylate BMD), a commonly used in-feed antibiotic, through Illumina sequencing of the internal transcribed spacer 2 (ITS2) region of fungal rRNA genes. Out of 124 samples sequenced, we identified a total of 468 unique fungal features that belong to four phyla and 125 genera in the GI tract. Ascomycota and Basidiomycota represented 90-99% of the intestinal mycobiota, with three genera including Microascus, Trichosporon, and Aspergillus accounting for over 80% of total fungal population in most GI segments. Furthermore, these fungal genera were dominated by Scopulariopsis brevicaulis, Trichosporon asahii and two Aspergillus species. We also revealed that the mycobiota are more diverse in the upper than lower GI tract. The cecal mycobiota transitioned from being S. brevicauli-dominant on day 14 to T. asahii-dominant on day 28. Furthermore, 2-week feeding of 55 mg/kg BMD tended to reduce the cecal mycobiota a- diversity. Taken together, we provided a comprehensive biogeographic view and succession pattern of the chicken intestinal mycobiota and its influence by BMD. A better understanding of intestinal mycobiota may lead to development of novel strategies to improve animal health and productivity. [ABSTRACT FROM AUTHOR]

Cathelicidins comprise a family of antimicrobial peptides sharing a highly conserved cathelin domain. Here we report that the entire chicken genome encodes three cathelicidins, namely fowlicidin-1 to -3, which are densely clustered within a 7.5-kb distance at the proximal end of chromosome 2p. Each fowlicidin gene adopts a four-exon, three-intron structure, typical for a mammalian cathelicidin. Phylogenetic analysis revealed that fowlicidins and a group of distantly related mammalian cathelicidins known as neutrophilic granule proteins are likely to originate from a common ancestral gene prior to the separation of birds from mammals, whereas other classic mammalian cathelicidins may have been duplicated from the primordial gene for neutrophilic granule proteins after mammals and birds are diverged. Similar to ovine cathelicidin SMAP-29, putatively mature fowlicidins displayed potent and salt-independent activities against a range of Gram-negative and Gram-positive bacteria, including antibiotic-resistant strains, with minimum inhibitory concentrations in the range of 0.4–2.0 μM for most strains. Fowlicidin-1 and -2 also showed cytotoxicity, with 50% killing of mammalian erythrocytes or epithelial cells in the range of 6 – 40 μM. In addition, two fowlicidins demonstrated a strong positive cooperativity in binding lipopolysaccharide (LPS), resulting in nearly complete blockage of LPS-mediated proinflammatory gene expression in RAW264.7 cells. Taken together, fowlicidin-1 and -2 are clearly among the most potent cathelicidins that have been reported. Their broad spectrum and salt-insensitive antibacterial activities, coupled with their potent LPS-neutralizing activity, make fowlicidins excellent candidates for novel antimicrobial and antisepsis agents. [ABSTRACT FROM AUTHOR]