Prolonged repeated inseminations trigger a local immune response and accelerate aging of the uterovaginal junction in turkey hens

Artificial insemination is a standard practice in the turkey breeder industry to ensure the production of fertile eggs. Even though hens are inseminated on a weekly basis, their fertility tends to decline after a few weeks of production. Avian species have a specialized structures called sperm storage tubules (SSTs), located in the uterovaginal junction (UVJ) of the oviduct. The ability of SSTs to store sperm is directly correlated with the fertility of the hen. The objective of the study was to examine changes in the transcriptome of the turkey hen’s UVJ in response to the presence of sperm at three key stages of production. We hypothesized that repeated and prolonged exposure to sperm would alter the transcriptome of the UVJ. Samples were collected from virgin hens prior to the onset of lay, as well as from sham-inseminated (extender only) and semen-inseminated hens at early lay, peak lay, and late lay. Gene expression profiling of the UVJ was examined, and a differential expression analysis was conducted through pairwise comparisons between semen- and sham-inseminated groups at each production stage and across production stages. In the early laying stage, no significant gene expression changes were found between semen- and sham-inseminated groups. However, at peak lay, genes related to lipid biosynthesis, Wnt signaling, cell proliferation, and O-glycan biosynthesis were upregulated in the semen group, while the immune response and cytokine-cytokine receptor interaction were downregulated. In the late lay stage, the transcription pathway was upregulated in the semen group, whereas the translation pathway was downregulated. The local immune response that was suppressed during peak lay was increased at the late laying stage. In the semen-inseminated group, the UVJ exhibited advanced aging at the late laying stage, evidenced by reduced telomere maintenance and translation processes. The results from this study provide valuable insights into the alteration of the UVJ function in response to the presence of sperm at different stages of production and throughout the production cycle. Targeting the modulation of local immune response and addressing aging processes after peak production could potentially prevent or delay the decline in fertility of turkey breeder hens

Non‐canonical autophagy functions of ATG16L1 in epithelial cells limit lethal infection by influenza A virus

Influenza A virus (IAV) and SARS-CoV-2 (COVID-19) cause pandemic infections where cytokine storm syndrome and lung inflammation lead to high mortality. Given the high social and economic cost of respiratory viruses, there is an urgent need to understand how the airways defend against virus infection. Here we use mice lacking the WD and linker domains of ATG16L1 to demonstrate that ATG16L1-dependent targeting of LC3 to single-membrane, non-autophagosome compartments - referred to as non-canonical autophagy - protects mice from lethal IAV infection. Mice with systemic loss of non-canonical autophagy are exquisitely sensitive to low-pathogenicity IAV where extensive viral replication throughout the lungs, coupled with cytokine amplification mediated by plasmacytoid dendritic cells, leads to fulminant pneumonia, lung inflammation and high mortality. IAV was controlled within epithelial barriers where non-canonical autophagy reduced IAV fusion with endosomes and activation of interferon signalling. Conditional mouse models and ex vivo analysis showed that protection against IAV infection of lung was independent of phagocytes and other leucocytes. This establishes non-canonical autophagy in airway epithelial cells as a novel innate defence that restricts IAV infection and lethal inflammation at respiratory surfaces

The WD and linker domains of ATG16L1 required for non-canonical autophagy limit lethal influenza A virus infection at epithelial surfaces

Phagocytosis and autophagy represent two evolutionarily ancient pathways that provide an important defense against infection by delivering pathogens to lysosomes for degradation. Phagocytosis and autophagy are linked by non-canonical autophagy pathways that conjugate LC3 to endo-lysosome compartments to facilitate phagosome maturation and lysosome fusion. A role for non-canonical autophagy in host defence is implied from cellular studies in vitro, but critically, these studies have rarely been extended to infection of model organisms with intact epithelial barriers and complex immune systems. To address this, we developed a mouse model with specific loss of non-canonical autophagy by removing the WD and linker domain of ATG16L1 required for recruitment of LC3 to endo-lysosome compartments. The mice retain the coiled-coiled domain of ATG16L1 required for conventional autophagy and maintain tissue and immunological homeostasis. Mice with systemic loss of non-canonical autophagy are exquisitely sensitive to low-pathogenicity murine-adapted influenza A virus leading to extensive viral replication throughout the lungs, cytokine dysregulation, fulminant pneumonia and lung inflammation leading to high mortality associated with virulent strains. Conditional mouse models and ex vivo analysis showed that protection against IAV infection of lung required non-canonical autophagy within epithelial barriers but was independent of phagocytes and other leukocytes. This establishes non-canonical autophagy pathways in epithelial cells as a novel innate defence mechanism that can restrict IAV infection at mucosal surfaces

Preharvest Escherichia coli o157:h7 vaccination of beef cattle: industry-wide acceptance through a beef production lifecycle approach

Doctor of PhilosophyDepartment of Diagnostic Medicine/PathobiologyDaniel U. ThomsonEscherichia coli O157:H7 is responsible for over 70,000 cases of human illness every year in the United States. Most cases occur in children under the age of five, the elderly, or other immune-compromised people. A small percentage of these cases will develop a life threatening complication, hemolytic uremic syndrome. Cattle are the reservoir host for E. coli O157:H7 and serve as the main source of contamination of meat products and other food sources. The beef cattle industry is diverse with producers caring for as few as one to as many as thousands of cattle. The first objective of this research was to examine three major production systems (conventional, organic, and natural) in the U.S. and the published performance effects of the various technologies used in each system. The second objective was to determine if a newly licensed E. coli O157:H7 SRP® (SRP) vaccine administered to cows pre-partum could achieve successful passive transfer in their offspring. The third objective was to determine if colostrum obtained from SRP vaccinated heifers could protect against an oral challenge with an E. coli K99+ strain. The fourth objective was to examine the shedding characteristics, health, and performance effects of calves born to SRP-vaccinated cows that also receive SRP vaccination themselves. The technologies used in conventional beef cattle production resulted in significant improvements in health and performance of beef cattle. Vaccinating cows pre-partum with SRP resulted in passive transfer in calves consuming their colostrum. Calves that achieved successful passive transfer shed less E. coli K99+ and had improved fecal consistency compared to placebo. When calves were vaccinated with SRP at branding, weaning, and arrival to the feedyard there was no difference in fecal E. coli O157:H7 shedding on arrival to the feedyard or at harvest. Vaccinating calves with SRP had no effects on performance or health outcomes. Vaccinating cattle with SRP may provide protection against other pathogenic E. coli strains and warrants further investigation. The timing of vaccination appears to be an important consideration in order to ensure maximum vaccine efficacy

Reduced redox potential of the cytosol is important for African swine fever virus capsid assembly and maturation

Assembly of African swine fever virus (ASFV) involves the transfer of the major capsid protein, p73, from the cytosol onto the cytoplasmic face of endoplasmic reticulum-derived membranes. During this process, the folding of p73 is dependent upon transient association with a specific viral chaperone, CAP80. The cell cytoplasm maintains high concentrations of reduced glutathione, leading to a reducing environment. Here, the effects of redox environment on the assembly of ASFV have been studied. Diamide, which oxidizes the cell cytosol, slowed the folding of p73 and prevented release from CAP80 and subsequent binding of p73 to membranes. Similarly, cell oxidation slowed the assembly of p73 molecules already bound to membranes into virus capsid precursors. Interestingly, addition of oxidized glutathione to newly assembled virus capsid precursors in vitro led to disassembly; however, virus particles released from cells were resistant to oxidized glutathione. These data show that assembly of ASFV requires the reducing environment that prevails in the cytosol, but as the virus matures, it becomes resistant to oxidation, possibly indicating preparation for release from the cell

The WD and linker domains of ATG16L1 required for non-canonical autophagy limit lethal respiratory infection by influenza A virus at epithelial surfaces

SummaryRespiratory viruses such as influenza A virus (IAV) and SARS-CoV-2 (Covid-19) cause pandemic infections where cytokine storm syndrome, lung inflammation and pneumonia lead to high mortality. Given the high social and economic cost of these viruses, there is an urgent need for a comprehensive understanding of how the airways defend against virus infection. Viruses entering cells by endocytosis are killed when delivered to lysosomes for degradation. Lysosome delivery is facilitated by non-canonical autophagy pathways that conjugate LC3 to endo-lysosome compartments to enhance lysosome fusion. Here we use mice lacking the WD and linker domains of ATG16L1 to demonstrate that non-canonical autophagy protects mice from lethal IAV infection of the airways. Mice with systemic loss of non-canonical autophagy are exquisitely sensitive to low-pathogenicity murine-adapted IAV where extensive viral replication throughout the lungs, coupled with cytokine amplification mediated by plasmacytoid dendritic cells, leads to fulminant pneumonia, lung inflammation and high mortality. IAV infection was controlled within epithelial barriers where non-canonical autophagy slowed fusion of IAV with endosomes and reduced activation of interferon signalling. This was consistent with conditional mouse models and ex vivo analysis showing that protection against IAV infection of lung was independent of phagocytes and other leukocytes. This establishes non-canonical autophagy pathways in airway epithelial cells as a novel innate defence mechanism that can restrict IAV infection and lethal inflammation at respiratory surfaces.</jats:p

Non‐canonical autophagy functions of ATG16L1 in epithelial cells limit lethal infection by influenza A virus

Influenza A virus (IAV) and SARS-CoV-2 (COVID-19) cause pandemic infections where cytokine storm syndrome and lung inflammation lead to high mortality. Given the high social and economic cost of respiratory viruses, there is an urgent need to understand how the airways defend against virus infection. Here we use mice lacking the WD and linker domains of ATG16L1 to demonstrate that ATG16L1-dependent targeting of LC3 to single-membrane, non-autophagosome compartments – referred to as non-canonical autophagy – protects mice from lethal IAV infection. Mice with systemic loss of non-canonical autophagy are exquisitely sensitive to low-pathogenicity IAV where extensive viral replication throughout the lungs, coupled with cytokine amplification mediated by plasmacytoid dendritic cells, leads to fulminant pneumonia, lung inflammation and high mortality. IAV was controlled within epithelial barriers where non-canonical autophagy reduced IAV fusion with endosomes and activation of interferon signalling. Conditional mouse models and ex vivo analysis showed that protection against IAV infection of lung was independent of phagocytes and other leucocytes. This establishes non-canonical autophagy in airway epithelial cells as a novel innate defence that restricts IAV infection and lethal inflammation at respiratory surfaces.ISSN:0261-4189ISSN:1460-207

Selectivity of diamond- and square-mesh codends in de deepwater crustacean trawl fishery off the Balearic Islands (western Mediterranean)

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