ObjectiveThis study aimed to evaluate bacterial and host factors causing a fever in cows with metritis. For that, we investigated uterine microbiota using a metagenomic sequencing of the 16S rRNA gene (Study 1), and immune response parameters (Study 2) in metritic cows with and without a fever.Principal Findings (Study1)Bacterial communities were similar between the MNoFever and MFever groups based on distance metrics of relative abundance of bacteria. Metritic cows showed a greater prevalence of Bacteroidetes, and Bacteroides and Porphyromonas were the largest contributors to that difference. A comparison of relative abundance at the species level pointed to Bacteroides pyogenes as a fever-related species which was significantly abundant in the MFever than the MNoFever and Healthy groups; however, absolute abundance of Bacteroides pyogenes determined by droplet digital PCR (ddPCR) was similar between MFever and MNoFever groups, but higher than the Healthy group. The same trend was observed in the total number of bacteria.Principal Findings (Study2)The activity of polymorphonuclear leukocyte (PMN) and the production of TNFα, PGE2 metabolite, and PGE2 were evaluated in serum, before disease onset, at 0 and 3 DPP. Cows in the MNoFever had decreased proportion of PMN undergoing phagocytosis and oxidative burst compared with the MFever. The low PMN activity in the MNoFever was coupled with the low production of TNFα, but similar PGE2 metabolite and circulating PGE2.Conclusion/SignificanceOur study is the first to show a similar microbiome between metritic cows with and without a fever, which indicates that the host response may be more important for fever development than the microbiome. Bacteroides pyogenes was identified as an important pathogen for the development of metritis but not fever. The decreased inflammatory response may explain the lack of a febrile response in the MNoFever group.
Our results support that HTR2C polymorphisms play a role in antipsychotic-induced metabolic disturbance. More association studies are needed to further elucidate association of different HTR2C polymorphisms and antipsychotic-induced metabolic disturbance.
Renal glomeruli are the primary target of injury in diabetic nephropathy (DN), and the glomerular podocyte has a key role in disease progression. To identify potential novel therapeutic targets for DN, we performed high-throughput molecular profiling of G protein-coupled receptors (GPCRs) using human glomeruli. We identified an orphan GPCR, Gprc5a, as a highly podocyte-specific gene, the expression of which was significantly downregulated in glomeruli of patients with DN compared with those without DN. Inactivation of Gprc5a in mice resulted in thickening of the glomerular basement membrane and activation of mesangial cells, which are two hallmark features of DN in humans. Compared with wild-type mice, Gprc5a-deficient animals demonstrated increased albuminuria and more severe histologic changes after induction of diabetes with streptozotocin. Mechanistically, Gprc5a modulated TGF- signaling and activation of the EGF receptor in cultured podocytes. Gprc5a has an important role in the pathogenesis of DN, and further study of the podocyte-specific signaling activity of this protein is warranted.
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