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Adipocytokines are the major secretory products of adipose tissue and potential markers of metabolism and inflammation. However, their association in host immune response against tuberculous lymphadenitis (TBL) disease is not known. Thus, we measured the systemic levels of adipocytokines in TBL (n = 44) and compared to pulmonary tuberculosis (PTB, n = 44) and healthy control (HC, n = 44) individuals. We also examined the pre and post-treatment adipocytokine levels in TBL individuals upon completion of standard anti-tuberculosis treatment (ATT). The receiver operating characteristics (ROC) were performed between TBL, PTB and HCs to find the potential discriminatory markers. Finally, principal component (PCA) analysis was performed to reveal the expression patterns of adipocytokines among study groups. Our results demonstrate that TBL is associated with significantly higher systemic levels of adipocytokines (except resistin) when compared with PTB and significantly lower levels when compared with HC (except adiponectin) individuals. Upon completion of ATT, the systemic levels of adiponectin and resistin were significantly decreased when compared to pre-treatment levels. Upon ROC analysis, all the three adipocytokines discriminated TBL from PTB but not with HCs, respectively. Similarly, adipocytokines were differentially clustered in TBL in comparison to PTB in PCA analysis. Therefore, adipocytokines are a distinguishing feature in TBL compared to PTB individuals. [ABSTRACT FROM AUTHOR]

Tuberculous lymphadenitis (TBL) is defined by reduced proinflammatory cytokines and elevated CD4+, CD8+ T cells and decreased CD8+ cytotoxic markers. However, ex-vivo phenotyping of diverse leucocytes in TBL has not been done. We show activated and atypical B cells, myeloid dendritic cells (mDCs), classical, non-classical and intermediate monocytes, T regulatory (T regs) cells, CD4+ T cell effector memory RA (TEMRA), CD4+ effector and CD8+ central memory phenotypes were significantly increased in TBL compared to LTB individuals. In contrast, classical memory and plasma B cells, plasmacytoid DCs (pDCs), CD8+ TEMRA, CD4+ naïve and central memory cells were significantly decreased in TBL compared to LTB individuals. Some of the leucocyte frequencies (atypical memory B cells, pDCs, myeloid-derived suppressor cells, CD4+ effector and CD8+ central memory was increased; activated memory and plasma B cell, mDCs, classical, non-classical, intermediate monocytes, T regs, CD4+ TEMRA, CD4+, CD8+ naïve and effector memory cells and CD8+ central memory cells were decreased) were significantly modulated after anti-TB treatment among TBL individuals. UMAP analysis show that leucocyte subsets or islands expressing specific markers were significantly different in TBL baseline and post-treatment individuals. Overall, we suggest altered frequencies of diverse leucocytes influences the disease pathology and protective immunity in TBL individuals. [ABSTRACT FROM AUTHOR]

Pulmonary tuberculosis is associated with higher plasma levels of antimicrobial peptides (AMPs) and lower granulysin levels. However, the association of AMPs with tuberculous lymphadenitis (TBL) is not well studied. Hence, we measured the plasma levels of human beta defensin-2 (HBD2), granulysin, human neutrophil peptides 1–3 (HNP1-3) and cathelicidin (LL37) in TBL compared to latent tuberculosis (LTB) and healthy controls (HC) and in TBL individuals upon completion of anti-tuberculosis treatment (ATT). We examined the association of AMPs with TBL lymph node culture grade or lymph node involvement. Finally, the discriminatory potential of these proteins was assessed using receiver operating characteristic (ROC) analysis. TBL individuals display significantly diminished circulating levels of AMPs (granulysin and HNP1-3) but not HBD-2 and LL-37 in comparison to LTB and HCs. Similarly, after ATT, both HBD-2 and HNP1-3 were significantly elevated and LL-37 was significantly reduced in TBL individuals. Granulysin and HNP1-3 discriminates TBL from LTB and HC individuals upon ROC analysis. AMPs did not exhibit significant correlation either with lymph node culture grades or lymph node involvement. Overall, TBL individuals show decreased AMPs and their reversal after ATT suggesting their association with underlying immune alteration in this poorly studied form of TB disease. [ABSTRACT FROM AUTHOR]

Tuberculous lymphadenitis (TBL) is associated with the expansion of CD4+ and CD8+ T cells expressing Type 1 and Type 17 cytokines in the peripheral blood. However, the expression pattern of cytokine producing natural killer (NK) cells in both the peripheral blood and affected lymph nodes i.e. site of infection in TBL have not been examined. Hence, we have analyzed the baseline and mycobacterial antigen specific NK cell cytokine frequencies in whole blood of TBL and pulmonary tuberculosis (PTB) individuals. We have also examined the NK cell frequencies before and after treatment completion and in peripheral blood versus affected lymph nodes (LN) of TBL individuals. TBL is characterized by diminished frequencies of NK cells expressing Type 1 (IFNγ, TNFα), Type 17 (IL-17F) cytokines compared to PTB individuals upon antigen-specific stimulation. In contrast, TBL individuals did not exhibit any significant differences in the frequencies of NK cells expressing Type 1 and Type 17 cytokines upon completion of anti-tuberculosis treatment. LN of TBL is associated with altered frequencies of NK cells expressing Type 17 (increased IL-17F and decreased IL-22) cytokines when compared to peripheral blood. Thus, we conclude that TBL individuals are characterized by diminished frequencies of NK cells expressing Type 1/Type 17 cytokines. [ABSTRACT FROM AUTHOR]