MUSCULAR TUBERCULOSIS: RARE PRESENTATION OF A COMMON ENTITY

Tuberculosis is a global health problem mainly affecting people in developing countries although muscular involvement is rarely seen. Authors hereby, describe a case of tuberculosis of triceps muscle in a 35-year-old immunocompetent female who presented with swelling in right upper arm. Radiological examination ruled out involvement of underlying bones. Excision biopsy was performed and on histopathological examination cyst wall showed presence of foamy macrophages in sheets, inammatory cells and few scattered epithelioid cells but no well-formed granulomas or giant cells were seen. ZN stain for acid fast bacilli was positive. Based on the above ndings a diagnosis of tuberculosis of triceps muscle was made. The patient responded well to antituberculosis therapy and is currently on follow up.

Targeting Molecular Inflammatory Pathways in Granuloma as Host-Directed Therapies for Tuberculosis

Globally, more than 10 million people developed active tuberculosis (TB), with 1.4 million deaths in 2020. In addition, the emergence of drug-resistant strains in many regions of the world threatens national TB control programs. This requires an understanding of host-pathogen interactions and finding novel treatments including host-directed therapies (HDTs) is of utter importance to tackle the TB epidemic. Mycobacterium tuberculosis (Mtb), the causative agent for TB, mainly infects the lungs causing inflammatory processes leading to immune activation and the development and formation of granulomas. During TB disease progression, the mononuclear inflammatory cell infiltrates which form the central structure of granulomas undergo cellular changes to form epithelioid cells, multinucleated giant cells and foamy macrophages. Granulomas further contain neutrophils, NK cells, dendritic cells and an outer layer composed of T and B lymphocytes and fibroblasts. This complex granulomatous host response can be modulated by Mtb to induce pathological changes damaging host lung tissues ultimately benefiting the persistence and survival of Mtb within host macrophages. The development of cavities is likely to enhance inter-host transmission and caseum could facilitate the dissemination of Mtb to other organs inducing disease progression. This review explores host targets and molecular pathways in the inflammatory granuloma host immune response that may be beneficial as target candidates for HDTs against TB.

Ang II-Induced Hypertension Exacerbates the Pathogenesis of Tuberculosis

It has been known that infection plays a role in the development of hypertension. However, the role of hypertension in the progression of infectious diseases remain unknown. Many countries with high rates of hypertension show geographical overlaps with those showing high incidence rates of tuberculosis (TB). To explore the role of hypertension in tuberculosis, we compared the effects of hypertension during mycobacterial infection, we infected both hypertensive Angiotensin II (Ang II) and control mice with Mycobacterium tuberculosis (Mtb) strain H37Ra by intratracheal injection. Ang II-induced hypertension promotes cell death through both apoptosis and necrosis in Mtb H37Ra infected mouse lungs. Interestingly, we found that lipid accumulation in pulmonary tissues was significantly increased in the hypertension group compared to the normal controls. Ang II-induced hypertension increases the formation of foamy macrophages during Mtb infection and it leads to cell death. Moreover, the hypertension group showed more severe granuloma formation and fibrotic lesions in comparison with the control group. Finally, we observed that the total number of mycobacteria was increased in the lungs in the hypertension group compared to the normal controls. Taken together, these results suggest that hypertension increases intracellular survival of Mtb through formation of foamy macrophages, resulting in severe pathogenesis of TB.

Cerebrotendinous xanthomatosis with radiological abnormalities of the chest

A 55-year-old man with mental retardation and calcaneal tendon thickening was referred for a suspected genetic disease. His serum cholestanol was elevated and genetic analysis of his blood cells for CYP27A1 revealed a homozygous missense mutation. We diagnosed him with cerebrotendinous xanthomatosis (CTX). Chest radiography revealed diffuse micronodular and reticular opacities. Histological findings obtained from the transbronchial lung biopsy revealed foamy macrophages and multinucleate giant cells with marked lipid crystal clefts. Although there are few reports of pulmonary lesions in CTX, we concluded from the radiological and histopathological findings that the pulmonary lesions were indeed caused by the CTX. The patient was treated with chenodeoxycholic acid. His neurological findings and calcaneal tendon thickening were unchanged; however, his serum cholestanol and radiological abnormalities of the chest decreased.

Macrophage-Mediated Tissue Response Evoked By Subchronic Inhalation of Lead Oxide Nanoparticles Is Associated With The Alteration of Phospholipases C And Cholesterol Transporters

BackgroundInhalation of lead oxide nanoparticles (PbO NPs), which are emitted to the environment by high-temperature technological processes, heavily impairs target organs. These nanoparticles pass through the lung barrier and are distributed via the blood into secondary target organs, where they cause numerous pathological alterations. Here, we studied in detail, macrophages as specialized cells involved in the innate and adaptive immune response in selected target organs to unravel their potential involvement in reaction to subchronic PbO NP inhalation. In this context, we also tackled possible alterations in lipid uptake in the lungs and liver, which is usually associated with foamy macrophage formation. MethodsFemale mice CD-1 (ICR), as a model organism, were placed into whole-body inhalation chambers and continuously exposed to PbO NPs at a concentration of 0.956 × 106 NPs/cm3 for 11 weeks (24/7). At the end of the exposure period, target organs (lung, liver, kidney, and spleen) were collected for analyses.ResultsThe histopathological analysis of PbO NP exposed lung revealed serious chronic inflammation of lung tissues. The number of foamy macrophages was significantly increased in lung, and they contained numerous cholesterol crystals. PbO NP inhalation induced changes in expression of phospholipases C (PLC) as enzymes linked to macrophage-mediated inflammation in lungs. In the liver, the subchronic inhalation of PbO NPs caused predominantly hyperemia, microsteatosis or remodeling of the liver parenchyma, and the number of liver macrophages was also significantly increased. The expression of a scavenger receptor CD36 and transporter ABCA1, which are associated with lipid metabolism, was significantly altered in the liver. No microscopic or serious functional kidney alterations were detected after subchronic PbO NP exposure and CD68 positive cells were present in the physiological mode in the interstitial tissues. ConclusionOur study determined the association of increased cholesterol and lipid storage in targeted tissues with the alteration of scavenger receptors and phospholipases C after subchronic inhalation of PbO NPs and uncovered processes, which contribute to steatosis in liver and foamy macrophages in lungs.

Immune Alveolitis in Interstitial Lung Disease: an Attractive Cytological Profile in Immunocompromised Patients.

Background: Bronchoalveolar lavage (BAL) is a major diagnostic tool in interstitial lung disease (ILD). Its use remains largely quantitative, usually focused on cell differential ratio. However, cellular morphological features provide additional valuable information. The significance of the "immune alveolitis" cytological profile, characterized by lymphocytic alveolitis with activated lymphocytes and macrophages in epithelioid transformation or foamy macrophages desquamating in cohesive clusters with lymphocytes, remains unknown in ILD. Our objective was to describe patients’ characteristics and diagnoses associated with an immune alveolitis profile in undiagnosed ILD.Methods: We performed a monocentric retrospective observational study. Eligible patients were adults undergoing diagnostic exploration for ILD and whose BAL fluid displayed an immune alveolitis profile. For each patient, we collected clinical, radiological and biological findings as well as the final etiology of ILD. Results: Between January 2012 and December 2018, 249 patients were included. Mean age was 57±16 years, 140 patients (56%) were men, and 65% of patients were immunocompromised. The main etiological diagnosis was Pneumocystis pneumonia (PCP) (24%), followed by drug-induced lung disease (DILD) (20%), viral pneumonia (14%) and hypersensitivity pneumonitis (HP) (10%). All PCP were diagnosed in immunocompromised patients while HP was found in only 8% of this subgroup. DILD and viral pneumonia were also commonly diagnosed in immunocompromised patients (94% and 80%, respectively).Conclusions: Our study highlights the additional value of BAL qualitative description in ILD. We suggest incorporating the immune alveolitis profile for the diagnosis and management of ILD, especially in immunocompromised patients, since it guides towards specific diagnoses.

Occurrence of foamy macrophages during the innate response of zebrafish to trypanosome infections

A tightly regulated innate immune response to trypanosome infections is critical to strike a balance between parasite control and inflammation-associated pathology. In this study, we make use of the recently established Trypanosoma carassii infection model in larval zebrafish to study the early response of macrophages and neutrophils to trypanosome infections in vivo. We consistently identified high- and low-infected individuals and were able to simultaneously characterize their differential innate response. Not only did macrophage and neutrophil number and distribution differ between the two groups, but also macrophage morphology and activation state. Exclusive to high-infected zebrafish, was the occurrence of foamy macrophages characterized by a strong pro-inflammatory profile and potentially associated with an exacerbated immune response as well as susceptibility to the infection. To our knowledge this is the first report of the occurrence of foamy macrophages during an extracellular trypanosome infection.