Endosomes are characterized by the presence of various phosphoinositides that are essential for defining the membrane properties. However, the interplay between endosomal phosphoinositides metabolism and innate immunity is yet to be fully understood. Here, our findings highlight the evolutionary continuity of RAB-10/Rab10's involvement in regulating innate immunity. Upon infection of Caenorhabditis elegans with Pseudomonas aeruginosa, an increase in RAB-10 activity was observed in the intestine. Conversely, when RAB-10 was absent, the intestinal diacylglycerols (DAGs) decreased, and the animal's response to the pathogen was impaired. Further research revealed that UNC-16/JIP3 acts as an RAB-10 effector, facilitating the recruitment of phospholipase EGL-8 to endosomes. This leads to a decrease in endosomal phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and an elevation of DAGs, as well as the activation of the PMK-1/p38 MAPK innate immune pathway. It is noteworthy that the dimerization of UNC-16 is a prerequisite for its interaction with RAB-10(GTP) and the recruitment of EGL-8. Moreover, we ascertained that the rise in RAB-10 activity, due to infection, was attributed to the augmented expression of LET-413/Erbin, and the nuclear receptor NHR-25/NR5A1/2 was determined to be indispensable for this increase. Hence, this study illuminates the significance of endosomal PI(4,5)P2 catabolism in boosting innate immunity and outlines an NHR-25-mediated mechanism for pathogen detection in intestinal epithelia.
Animals ; Caenorhabditis elegans/genetics* ; Endosomes/immunology* ; Caenorhabditis elegans Proteins/immunology* ; Phosphatidylinositol 4,5-Diphosphate/immunology* ; Immunity, Innate ; Pseudomonas aeruginosa/immunology* ; rab GTP-Binding Proteins/genetics* ; Diglycerides/metabolism*

Objective To investigate the clinical characteristics and risk factors of bacterial liver abscess (BLA) complicated with septicemia.Methods Fifty two BLA patients complicated with septicemia admitted in our hospital from January 2011 to December 2015 were retrospectively reviewed;and 52 cases of BLA without septicemia admitted at the same period were randomly selected as control group.The clinical manifestations, laboratory and radiographic findings, clinical outcome of these patients were analyzed.Logistic regression analysis was used to study the clinical features and risk factors of BLA complicated with septicemia.Results Compared to the control group, the BLA with septicemia group had higher prevalence rates in diabetes mellitus, malignant tumors, jaundice, albumin <35 g/L, BUN≥8.2 mmol/L, hyperglycemia, multiple abscesses and abscesses size ≥10 cm(P<0.05 or <0.01).The blood culture showed that K.pneumoniae(63.3%) was the most commonly isolated pathogen, followed by E.coli(16.7%).Univariate analysis revealed that diabetes mellitus(OR=2.200,95%CI 1.042-4.646), malignant tumors (OR=3.667,95%CI 1.023-13.143), albumin <35 g/ L(OR=2.800,95%CI 1.009-7.774), BUN≥8.2 mmol/L(OR=3.167,95%CI 1.265-7.929), hyperglycemia(OR=3.400,95%CI 1.254-9.216), multiple abscesses(OR=2.667,95%CI 1.043-6.815), abscesses size≥10 cm (OR=5.000,95%CI 1.096-22.820) were positively associated with bacterial liver abscess complicated with septicemia.Multivariate Logistic regression showed that abscesses size≥10 cm (OR=14.016,95%CI 1.354-145.070) was an independent risk factor for complication of with septicemia.Conclusion septicemia is a common complication for bacterial liver abscess, clinically effective measures shauld be taken to prevent and control risk factors associated with septicemia.