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Tuberculosis (TB) is a serious public health problem in Bangladesh. National tuberculosis control program recognizes that almost half of the TB cases remain undiagnosed in the country. To increase case detection rate, it is very important to familiarize the physicians with unusual presentation of TB. We describe a 51 years old woman with a past medical history of Hypertension (HTN), Type 2 Diabetes Mellitus (DM), and Nonalcoholic steatohepatitis-chronic liver disease (NASH-CLD) who presented to us with low grade fever, anorexia, nausea, and recurrent vomiting for one month. Physical examination and laboratory tests revealed no significant abnormalities and symptoms were treated symptomatically. After about two months, the condition did not improve. All routine blood biochemistry and imaging reports were not suggestive of any disease except for high ESR and abnormal LFT (mild increase in ALP, ALT and moderate increase in GGTP). To exclude the differential diagnoses (such as abdominal TB), we advised computed tomography (CT) scan of chest and abdomen but the results came out normal. Her PPD came out positive but it was not confirmatory of TB as the patient was previously vaccinated with BCG vaccine. As the patient was immune-compromised we suggested starting Anti-TB drugs based on clinical judgment and in the context of Bangladesh being a TB endemic area. But the patient was not convinced to take anti-Tb drugs without definite diagnosis. After another month of persistent symptoms a repeat CT of the chest was advised that revealed multiple enlarged mediastinal lymph-nodes. As the patient had a history of CLD and high PT, Fine Needle Aspiration Cytology (FNAC) was deferred. Patient was started on Anti tubercular treatment and symptoms subsided within three weeks. Treatment was continued for one year. This case summarizes the unusual presentation of mediastinal lymph node Tuberculosis in an adult., Competing Interests: Declaration of Competing Interest All authors have none to declare., (Copyright © 2020 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.)

Immune responses were assessed at the single-cell level in lymph nodes from children with tuberculous lymphadenitis. Tuberculosis infection was associated with tissue remodeling of lymph nodes as well as altered cellular composition. Granulomas were significantly enriched with CD68+ macrophages expressing the M. tuberculosis complex-specific protein antigen MPT64 and inducible nitric oxide synthase. There was a significant increase in CD8+ cytolytic T cells surrounding the granuloma; however, CD8+ T cells expressed low levels of the cytolytic and antimicrobial effector molecules perforin and granulysin in the granulomatous lesions. Quantitative real-time mRNA analysis revealed that interferon-gamma, tumor necrosis factor-alpha, and interleukin-17 were not up-regulated in infected lymph nodes, but there was a significant induction of both transforming growth factor-beta and interleukin-13. In addition, granulomas contained an increased number of CD4+FoxP3+ T cells co-expressing the immunoregulatory cytotoxic T-lymphocyte antigen-4 and glucocorticoid-induced tumor necrosis factor receptor molecules. Low numbers of CD8+ T cells in the lesions correlated with high levels of transforming growth factor-beta and FoxP3+ regulatory T cells, suggesting active immunosuppression at the local infection site. Compartmentalization and skewing of the immune response toward a regulatory phenotype may result in an uncoordinated effector T-cell response that reduces granule-mediated killing of M. tuberculosis-infected cells and subsequent disease control.

Multi-colour flow cytometry was applied to determine T-cell-specific interferon-gamma, interleukin-2 and tumour necrosis factor-alpha expression in children with tuberculosis and non-tuberculosis mycobacterial lymphadenopathy (NTM-L). In vitro stimulation of peripheral blood mononuclear cells with purified protein derivative from Mycobacterium tuberculosis (tuberculin) and M. avium (sensitin) revealed differential recognition of tuberculin and sensitin in both study groups. Ratios of tuberculin-specific and sensitin-specific T-cell proportions in individual patients discriminated between children with tuberculosis or NTM-L. These findings have the potential to improve the differential diagnosis of mycobacterial infections.

Background: The immune response to Mycobacterium tuberculosis is complex and multifactorial, the cytokine system being a major factor in M. tuberculosis immunity., Aim: To analyze the immunohistochemical aspects of tuberculous lymph nodes in immunocompetent patients and search for associations between SOCS and cytokine expression in human tuberculous lymphadenitis., Methods: Thirteen lymph nodes were assayed by immunohistochemistry for SOCS-1 and 3, STAT-3, RANTES, MIP-1-alpha, ICAM-1, IFN-gamma as well as CD45RO, CD20, CD34, CD68, trypsin and lysozyme. Additionally, the RT in situ PCR was performed for SOCS-1 and 3 mRNA detection., Results: Decreased MIP-1 alpha expression together with reduced SOCS-3 (p=0.042), lysozyme (p=0.024) and CD45RO (p=0.05) was observed in the TB lymph nodes compared to the control lymph nodes. In conclusion, the lymphadenitis due to M. tuberculosis was associated with a downregulation of memory T cells (CD45RO), activated lysozymes and SOCS-3 compared to controls, which may play a role in the long-term bacterial replication and altered immune modulation characteristic of the disease.

Inflammatory cells in lymph nodes of eighteen patients suffering from culture-proven tuberculous lymphadenitis were examined by histological and immunohistochemical techniques. Ten patients suffered from symptomatic HIV-infection and eight patients were immunocompetent individuals without HIV-1 serology. Characteristic granulomas with or without caseation were observed in eight immunocompetent and four HIV-1-infected patients with less marked lymphopenia of CD4 positive peripheral blood lymphocytes. No epitheloid cell formation was present in lymph nodes of HIV1-infected patients with more severe depression of CD4 positive peripheral blood lymphocyte count. Foamy macrophages were found instead of these cells. While many cells--predominantly lymphocytes--express CD25 (IL-2 receptor) in cases with typical epitheloid granulomas there is no such CD25 expression in cases without any epitheloid cell formation. This result suggest that T cell function is necessary for epitheloid granuloma formation in human tuberculosis. The phenotype of macrophages underwent progressive changes parallel to decreasing numbers of CD4 positive peripheral blood lymphocytes. Foamy macrophages in Mycobacterium avium-intracellulare infection represented an end-stage phenotype. They were positive for S100 protein and they did not express lysozyme, alpha-1-anti-chymotrypsin, L1 antigen (Mac387) and CD4, whereas positivity for HLA-DR, CD68 and Ki-M8 was preserved. In situ immunohistochemical demonstration of IFN-alpha, IFN-beta, TNF-alpha, IL-1 and IL-6 revealed that foamy cells in M. tuberculosis infection were highly active effector cells. They contained higher concentrations of the examined cytokines than epitheloid cells in the lesions of HIV+ and HIV-patients. Corresponding to these findings the histological proof of acid-fast bacilli was generally not successful in typical HIV-associated tuberculosis. The foamy appearance may result from the lipid-rich cell membranes of destroyed acid-fast bacilli. In contrast acid-fast bacilli-packed foamy macrophages in AIDS patients with M. avium-intracellulare (MAI) infection did not produce any of the examined cytokines.

The phenotype of inflammatory cells in lymph nodes from 16 patients with culture-proven tuberculous lymphadenitis were examined by histological and immunohistochemical techniques. Eight patients were suffering from a symptomatic HIV1 infection and 8 patients were immunocompetent individuals without positive HIV1 serology. In addition, the lymph nodes of 2 AIDS patients with Mycobacterium avium-intracellulare infection were examined using the same techniques. Characteristic granulomas with or without caseation were observed in the 8 immunocompetent and the 4 HIV1-infected patients with less marked lymphopenia of CD4+ peripheral blood lymphocytes (PBL). In lymph nodes from the other HIV1-infected patients with more severe depression of CD4+ PBL, no epithelioid cell formation was present; instead, foamy macrophages were found. The phenotype of the macrophages underwent progressive changes in parallel with the decreasing numbers of CD4+ PBL. Foamy macrophages in M. avium-intracellulare infection exhibited remarkable erythrophagocytotic activity and may represent an end-stage phenotype. They were positive for S100 protein and did not produce lysozyme or alpha-1-antichymotrypsin. They lost the antigen which was detected by monoclonal antibody Mac387 whereas positivity for HLA-DR, CD68 and KI-M8 was preserved. While many lymphocytes expressed CD25 (IL2 receptor) in cases with typical granulomas, there was no such CD25 expression in cases without epithelioid cell formation. Although granulomas have been produced in experimental animals independently of cell-mediated immune mechanisms, our results suggest that T-cell functions are necessary for epithelioid granuloma formation in human tuberculosis.

Since the recent extensive domestication and farming of deer in New Zealand, tuberculosis (Tb) has presented a major health issue in farmed herds. The spectrum of disease pathology and immune reactivity in this naturally infected species represents a potentially valuable large animal model for the study of the underlying immunological and pathological mechanisms involved in Mycobacterium bovis infection and its spread. A combination of laboratory assays for the detection of tuberculosis in deer is described. Domesticated deer are genetically diverse and their exposure to natural variations in environmental conditions results in a spectrum of immune responses and pathology of Tb, similar to that found in man. The model has special relevance to the study of host responses to tuberculosis in immunocompromised individuals, particularly those in the third world. Elucidation of the mechanisms involved in immune responses to Tb in deer will facilitate the development of vaccines and improved diagnostic assays for Tb in man.