Legionella pneumonia: A Case of Fever Prolonged for 10 Days.

Legionnaires' disease is a potentially severe type of pneumonia most often caused by the organism Legionella pneumophila. Exposure to this bacterial pathogen typically happens in the community but may also occur in the hospital setting. This report describes the case of a patient who presented due to 10 days of fever, shortness of breath, and diarrhea, with initial imaging demonstrating multifocal pneumonia. The patient was appropriately started on empiric antibiotics for community-acquired pneumonia and admitted to the medicine floor. The patient showed no meaningful improvement in his initial hospital course on empiric antibiotics with continued oxygen requirements. Meanwhile, urine Legionella antigen testing returned positive on hospital day four, and after tailoring antibiotics accordingly, the patient's clinical status improved significantly. This case report highlights the efficacy of broad testing in the initial admission and the need for constant re-evaluation in the context of a patient not improving with appropriate therapy.

Acute exposure of minimally oxLDL elicits survival responses by downregulating the mediators of NLRP3 inflammasome in cultured RAW 264.7 macrophages.

Lipid burden in macrophages driven by oxidized low-density lipoprotein (oxLDL) accelerates the foam cell formation and the activation of sterile inflammatory responses aggravating the atherosclerosis. However, there is limited information on the mediators and the pathways involved in the possible survival responses, especially at the initial phase, by lipid burden in macrophage cells on encountering oxLDL. The present study was designed to assess the expression status of major mediators involved in the NLRP3 inflammasome pathway of sterile inflammation and the cellular responses in oxLDL-challenged cultured RAW 264.7 macrophage cells. OxLDL-treated RAW 264.7 macrophage cells displayed a decreased expression of the key sterile inflammatory mediators, TLR4, TLR2, ASC, NLRP3 and IL-18 at protein and transcript levels; however, they displayed increased level of IL-1ß, RAGE and TREM1 at protein level. Biological responses including lipid uptake, lipid peroxidation, cellular hypertrophy, mitochondrial density and mitochondrial membrane potential were significantly increased in oxLDL-treated macrophages. Moreover, superoxide production was significantly decreased in the oxLDL-treated macrophages compared to the control. Overall, the findings revealed the expression status of key sterile mediators and the macrophage response during the initial phase of oxLDL exposure tend towards the prevention of inflammation. Further understanding would open novel translational opportunities in the management of atherosclerosis.

Mitochondrial DAMPs and altered mitochondrial dynamics in OxLDL burden in atherosclerosis.

Atherosclerosis results in life-threatening cardiovascular pathologies, including ischemic heart disease, stroke, myocardial infarction, and peripheral arterial disease. The role of increased serum low-density lipoprotein (LDL) and resultant accumulation of oxidized-LDL (oxLDL) in atheroma formation is well established. Recent findings elucidate the significance of mitochondrial damage-associated molecular patterns (mtDAMPs) in triggering sterile inflammation in concert with oxLDL. The mtDAMPs including mitochondrial DNA (mtDNA), cytochrome C, cardiolipin, heat shock protein 60 (HSP60), mitochondrial transcription factor A (TFAM), and N-formyl peptides, are expected to possess proatherogenic roles. However, limited data are available in the literature. The mtDAMPs initiate sterile inflammation in atherosclerotic lesions via numerous signaling pathways, most of which converge to the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome. Priming the activation of the NLRP3 inflammasome, mtDAMPs promote secretion of proinflammatory cytokines, including interleukin-1ß (IL-1ß), implicated in atherosclerotic lesions through vascular smooth muscle and fibroblast proliferation, arterial wall thickening, and plaque formation. In this article we critically reviewed and discussed the central role of the NLRP3 inflammasome in mtDAMP-induced sterile inflammation in atherosclerosis with specific components including caspase-1, pregnane X receptor (PXR), adenosine monophosphate activated protein kinase (AMPK), protein phosphatase 2A (PP2A), thioredoxin-interacting protein (TXNIP), and downstream cytokines including IL-1ß and IL-18 as potential mediators of atherosclerosis. Better understanding of the proinflammatory effects of mtDAMPs and its pathological association with oxLDL possess immense translational significance for novel therapeutic intervention.