Large-Scale Gene Expression Signatures Reveal a Microbicidal Pattern of Activation in Mycobacterium leprae-Infected Monocyte-Derived Macrophages With Low Multiplicity of Infection

Leprosy is a disease with a clinical spectrum of presentations that is also manifested in diverse histological features. At one pole, lepromatous lesions (L-pole) have phagocytic foamy macrophages heavily parasitized with freely multiplying intracellular Mycobacterium leprae. At the other pole, the presence of epithelioid giant cells and granulomatous formation in tuberculoid lesions (T-pole) lead to the control of M. leprae replication and the containment of its spread. The mechanism that triggers this polarization is unknown, but macrophages are central in this process. Over the past few years, leprosy has been studied using large scale techniques to shed light on the basic pathways that, upon infection, rewire the host cellular metabolism and gene expression. M. leprae is particularly peculiar as it invades Schwann cells in the nerves, reprogramming their gene expression leading to a stem-like cell phenotype. This modulatory behavior exerted by M. leprae is also observed in skin macrophages. Here, we used live M. leprae to infect (10:1 multiplicity of infection) monocyte-derived macrophages (MDMs) for 48 h and analyzed the whole gene expression profile using microarrays. In this model, we observe an intense upregulation of genes consistent with a cellular immune response, with enriched pathways including peptide and protein secretion, leukocyte activation, inflammation, and cellular divalent inorganic cation homeostasis. Among the most differentially expressed genes (DEGs) are CCL5/RANTES and CYP27B1, and several members of the metallothionein and metalloproteinase families. This is consistent with a proinflammatory state that would resemble macrophage rewiring toward granulomatous formation observed at the T-pole. Furthermore, a comparison with a dataset retrieved from the Gene Expression Omnibus of M. leprae-infected Schwann cells (MOI 100:1) showed that the patterns among the DEGs are highly distinct, as the Schwann cells under these conditions had a scavenging and phagocytic gene profile similar to M2-like macrophages, with enriched pathways rearrangements in the cytoskeleton, lipid and cholesterol metabolism and upregulated genes including MVK, MSMO1, and LACC1/FAMIN. In summary, macrophages may have a central role in defining the paradigmatic cellular (T-pole) vs. humoral (L-pole) responses and it is likely that the multiplicity of infection and genetic polymorphisms in key genes are gearing this polarization.

Mycobacterium Spindle Cell Pseudotumor Caused by Mycobacterium xenopi: A First Described Association of a Rare Entity Presenting in the Lung

Mycobacterial spindle cell pseudotumor (MSP) is a rare benign lesion characterized by a proliferation of bland spindle-shaped histiocytes with vague granulomatous formation, positive for acid-fast bacilli staining. This lesion is usually reported in the lymph nodes and skin of immunocompromised patients; only 6 cases primary in the lung have been reported in the English literature to this date. In this article, we present the case of a 42-year-old female status post failed kidney-pancreas transplant with subsequent multiple kidney transplants, on chronic immunosuppression, who developed a mass in the left lower lobe consistent with MSP. Mycobacterium xenopi was identified in lung tissue culture, an association never previously described in literature. This case report alerts for the possible association of this rare form of non-tuberculous mycobacteria in the pathogenesis of MSP and highlights the importance of this differential diagnosis in lung masses of immunocompromised patients.

Small fibre neuropathy in sarcoidosis

Sarcoidosis is characterized by multisystem granulomatous formation particularly in the chest. In this case report, we present an uncommon case highlighting significant peripheral nerve involvement, a phenomenon that is not well recognized in sarcoidosis. The patient presented with severe incapacitating pain. Sarcoidosis as being the underlying cause was only established after extensive investigations. This case highlights the importance of recognizing small fibre peripheral polyneuropathy as a possible presentation of sarcoidosis. This could help to direct appropriate medical intervention.

Unexpected diagnosis in a patient with a liver mass: A case report

Sarcoidosis is a rare inflammatory disease. It is characterized by granulomatous formation. The liver is the second most common site of involvement after the lung. Sarcoidosis of the liver is usually asymptomatic. Symptomatic cases can present with jaundice, itching, elevated liver enzymes, and in rare situations, the development of portal hypertension. We, at this moment, submit a case of liver sarcoidosis in a patient with liver cirrhosis that presented with upper gastrointestinal bleeding. Upper digestive endoscopy revealed gastric varices. Ultrasonography of the abdomen revealed a liver mass that was suspicious for hepatocellular carcinoma. There is no nay cause of gastric varix in this patient apart from hepatic sarcoidosis (portal hypertension). Treatment of the patient with corticosteroids leads to the complete disappearance of the liver mass. Despite the high incidence of HCC in Egypt due to the high prevalence of HCV infection, it is crucial to search for the rare causes of hepatic masses. Keywords: liver mass; sarcoidosis, gastric varix

Post-stapedectomy reparative granuloma: a misnomer

The pathophysiology of so-called ‘reparative granuloma’ occurring after stapedectomy has not been determined and universally accepted management of this rare complication has not yet been established. A case is presented in which a mass developed in the middle ear after the use of a fat/wire prosthesis in a stapedectomy. Histological assessment revealed nonspecific granulation tissue and fat necrosis. It is suggested that ‘reparative granuloma’ is a misnomer as there is no microscopic evidence in this case nor in the literature of granulomatous formation. The condition may follow stapedectomy or stapedotomy. Furthermore, the name leads to confusion with a different condition, giant cell reparative granuloma, which involves the jaws and rarely the temporal bone. An alternative name, ‘Stapes surgery induced granulation tissue’ (SSIG) is therefore suggested for this condition.

Immunopathology of Schistosoma mansoni infection in rabbits: (A preliminary report)

Five rabbits infected with Schistosoma mansoni showed marked resistance, which resulted in low worm recovery and low egg production. Pathological changes appeared in liver and intestines as scattered foci of eosinophilic infiltration around immature eggs, with only occasional granulomatous formation. Antibodies to ovular and adult worm structures were demonstrated by immunofluorescence in the sera of rabbits prior to infection (natural antibodies) and specially following infection by S. mansoni. These findings point out to the peculiarities of the immunopathology of schistosomiasis in rabbits.