Fatal hepatic mucormycosis in an allogeneic hematopoietic-stem cell transplanted patient: Case report of a rare presentation and review of the literature.

Hepatic mucormycosis is a rare condition. Our objective is to report a case in a HSCT patient and to perform a review of the literature. A 36-year-old man with acute myeloid leukemia, performed a haploidentical HSCT. In D+132, when treating acute GVHD with methylprednisolone and etanercept, a hepatic abscess was diagnosed. Puncture of the abscess was performed, and fungal hyphae were visualized. The culture of the aspirate identified Mucor sp. Sequencing confirmed the isolate as Mucor indicus. The patient died despite the use of Amphotericin B. Our search identified 24 hepatic mucormycosis reports. Fifteen (62.5 %) were male and 79.1 % were immunocompromised. Fever accompanied with abdominal pain was present in 41.6 %. Twelve (50.0 %) had multiple hepatic lesions. Mortality rate was 45.8 % (n = 11/24). In conclusion, the most common clinical presentation of hepatic mucormycosis in immunocompromised patients might be abdominal pain and fever, along with hepatic abscess findings in abdominal imaging exams.

Bacterial sensing, cell signaling, and modulation of the immune response during sepsis.

Since the definition of systemic inflammatory response syndrome/sepsis was originally proposed, a large amount of new information has been generated showing a much more complex scenario of inflammatory and counterinflammatory responses during sepsis. Moreover, some fundamental mechanisms of sensing and destroying invading microorganisms have been uncovered, which include the discovery of TLR4 as the lipopolysaccharide (LPS) gene, implications of innate immune cells as drivers of the adaptive response to infection, and the modulation of multiple accessory molecules that stimulate or inhibit monocyte/macrophage and lymphocyte interactions. The complexity of the infection/injury-induced immune response could be better appreciated with the application of genomics and proteomics studies, and LPS was a useful tool in many of these studies. In this review, we discuss aspects of bacterial recognition and induced cellular activation during sepsis. Because of the relevance of endotoxin (LPS) research in the field, we focus on LPS and host interactions as a clue to understand microorganisms sensing and cell signaling, then we discuss how this response is modulated in septic patients.

Differential expression of toll-like receptor signaling cascades in LPS-tolerant human peripheral blood mononuclear cells.

Pre-exposure to low doses of LPS induces resistance to a lethal challenge, a phenomenon known as endotoxin tolerance. In this study, tolerance was induced in human PBMC by culturing cells with 1 ng/mL LPS for 48 h. Cells were subsequently challenged with 100 ng/mL LPS for 2, 6 and 24 h, and the expression of 84 genes encoding proteins involved in the TLR signaling pathway was evaluated at each time point by PCR array. LPS pretreatment did not modulate the expression of TLR4 and CD14 on the surface of monocytes. A gene was defined as tolerized when LPS pretreatment reversed the effect of LPS challenge on the expression of the gene or as non-tolerized when LPS pretreatment did not reverse the effects of LPS challenge. We observed impaired signal transduction through the NF-κB, JNK, ERK and TRIF pathways, whereas expression of p38 pathway-related genes was preserved in LPS-tolerant cells. These results show a distinct regulation of the TLR pathway cascades during tolerance; this may account for the differential gene expression of some inflammatory mediators, such as up-regulation of IL-10 and COX2 as well as down-regulation of TNF-α and IL-12. Depending on the effect of LPS-induced gene up-regulation or down-regulation, tolerance, as a reversion of such LPS effects, may result in repression or induction of gene expression.