ABSTRACT
Commensal intestinal protozoa, unlike their pathogenic relatives, are neglected members of the mammalian microbiome. These microbes have a significant impact on the host's intestinal immune homeostasis, typically by elevating anti-microbial host defense. Tritrichomonas musculis, a protozoan gut commensal, strengthens the intestinal host defense against enteric Salmonella infections through Asc- and Il1r1-dependent Th1 and Th17 cell activation. However, the underlying inflammasomes mediating this effect remain unknown. In this study, we report that colonization with T. musculis results in an increase in luminal extracellular ATP that is followed by increased caspase activity, higher cell death, elevated levels of IL-1ß, and increased numbers of IL-18 receptor-expressing Th1 and Th17 cells in the colon. Mice deficient in either Nlrp1b or Nlrp3 failed to display these protozoan-driven immune changes and lost resistance to enteric Salmonella infections even in the presence of T. musculis These findings demonstrate that T. musculis-mediated host protection requires sensors of extracellular and intracellular ATP to confer resistance to enteric Salmonella infections.
Subject(s)
Apoptosis Regulatory Proteins , Microbiota , NLR Family, Pyrin Domain-Containing 3 Protein , Tritrichomonas , Animals , Apoptosis Regulatory Proteins/immunology , Inflammasomes/metabolism , Interleukin-1beta/metabolism , Mammals/metabolism , Mice , NLR Family, Pyrin Domain-Containing 3 Protein/immunology , Symbiosis , Tritrichomonas/metabolismABSTRACT
Despite well-defined clinical and histopathological features of melanoma, atypical presentations mimicking other skin disorders can result in a delayed diagnosis or misdiagnosis and subsequent inappropriate treatment. Rosai-Dorfman disease (RDD) is a rare histiocytic disorder with unique clinical and histopathological features. We report a case of melanoma treated with cryotherapy that mimicked RDD both clinically and histopathologically. We compare this RDD-like melanoma to classic RDD, outlining the importance of clinicopathological correlation prior to treatment, as well as the potential pitfalls in diagnosis after cryotherapy of pigmented lesions.
Subject(s)
Histiocytosis, Sinus/diagnosis , Melanoma/diagnosis , Skin Neoplasms/diagnosis , Aged , Diagnosis, Differential , Female , Histiocytosis, Sinus/pathology , Humans , Melanoma/pathology , Skin Neoplasms/pathologyABSTRACT
PURPOSE: Currently no data exist to guide renal surgeons on the perioperative use of renin-angiotensin blockers despite potential cardiorenal benefits. We aimed to assess the impact of resuming renin-angiotensin blockers on postoperative renal function and adverse cardiac events following partial nephrectomy. MATERIALS AND METHODS: This is an observational analysis of patients who underwent robot-assisted laparoscopic partial nephrectomy from 2006 to 2014 at a single institution. The Wilcoxon rank sum and chi-square tests, and logistic regression were used to assess the risk of adverse renal and cardiac events stratified by history and pattern of renin-angiotensin blockade perioperatively. RESULTS: We identified 900 patients with a median followup of 16.3 months (IQR 1.4-39.1). There were no significant differences in severe renal dysfunction at last followup on univariate analysis or adverse cardiac events at 30 days on multivariate analysis in patients stratified by a history of renin-angiotensin blockade. Of the 338 patients 137 (41.9%) resumed renin-angiotensin blockade immediately after surgery, which did not result in any significant difference in the postoperative glomerular filtration rate (p >0.05). Resuming renin-angiotensin blockade at discharge home was associated with a decreased risk of heart failure within 30 days of surgery (0.3% vs 11.8% of cases) and stage IV/V chronic kidney disease at last followup (2.6% vs 25.5%, each p <0.001). CONCLUSIONS: Renin-angiotensin blockers appear safe to continue immediately after renal surgery. Discharge home with angiotensin converting enzyme inhibitors/angiotensin receptor blockers was associated with a decreased risk of heart failure and severe renal dysfunction. However, this risk may be overstated as a result of the small number of patients discharged without resuming the home medication.
Subject(s)
Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Cardio-Renal Syndrome/prevention & control , Laparoscopy/methods , Nephrectomy/methods , Robotic Surgical Procedures/methods , Aged , Female , Humans , Kidney Function Tests , Male , Middle Aged , Treatment OutcomeABSTRACT
Maintaining macrophage (MΦ) heterogeneity is critical to ensure intestinal tissue homeostasis and host defense. The gut microbiota and host factors are thought to synergistically guide intestinal MΦ development, although the exact nature, regulation, and location of such collaboration remain unclear. Here, we report that microbial biochemical energy metabolism promotes colony-stimulating factor 2 (CSF2) production by group 3 innate lymphoid cells (ILC3s) within solitary isolated lymphoid tissues (SILTs) in a cell-extrinsic, NLRP3/P2X7R-dependent fashion in the steady state. Tissue-infiltrating monocytes accumulating around SILTs followed a spatially constrained, distinct developmental trajectory into SILT-associated MΦs (SAMs). CSF2 regulated the mitochondrial membrane potential and reactive oxygen species production of SAMs and contributed to the antimicrobial defense against enteric bacterial infections. Collectively, these findings identify SILTs and CSF2-producing ILC3s as a microanatomic niche for intestinal MΦ development and functional programming fueled by the integration of commensal microbial energy metabolism.