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Article ; Online: Impact of diabetes mellitus on immunity to latent tuberculosis infection.

Kumar, Nathella Pavan / Babu, Subash

Frontiers in clinical diabetes and healthcare

2023 Volume 4, Page(s) 1095467

Abstract: Tuberculosis (TB) is an infectious disease that poses a major health threat and is one of the leading causes of death worldwide. Following exposure ... ...

Abstract	Tuberculosis (TB) is an infectious disease that poses a major health threat and is one of the leading causes of death worldwide. Following exposure to
Language	English
Publishing date	2023-01-26
Publishing country	Switzerland
Document type	Journal Article ; Review
ISSN	2673-6616
ISSN (online)	2673-6616
DOI	10.3389/fcdhc.2023.1095467
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Article ; Online: Biomarkers for Treatment Monitoring in Tuberculosis: A New Hope.

Babu, Subash

EBioMedicine

2017 Volume 26, Page(s) 13–14

MeSH term(s)	Antitubercular Agents ; Biomarkers ; Humans ; Tuberculosis
Chemical Substances	Antitubercular Agents ; Biomarkers
Language	English
Publishing date	2017-11-03
Publishing country	Netherlands
Document type	Journal Article ; Comment
ZDB-ID	2851331-9
ISSN	2352-3964
ISSN (online)	2352-3964
DOI	10.1016/j.ebiom.2017.11.002
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Article ; Online: Dominant expansion of CD4+, CD8+ T and NK cells expressing Th1/Tc1/Type 1 cytokines in culture-positive lymph node tuberculosis.

Kathamuthu, Gokul Raj / Sridhar, Rathinam / Baskaran, Dhanaraj / Babu, Subash

PloS one

2022 Volume 17, Issue 5, Page(s) e0269109

Abstract: Lymph node culture-positive tuberculosis (LNTB+) is associated with increased mycobacterial antigen-induced pro-inflammatory cytokine production compared to LN culture-negative tuberculosis (LNTB-). However, the frequencies of CD4+, CD8+ T cells and NK ... ...

Abstract	Lymph node culture-positive tuberculosis (LNTB+) is associated with increased mycobacterial antigen-induced pro-inflammatory cytokine production compared to LN culture-negative tuberculosis (LNTB-). However, the frequencies of CD4+, CD8+ T cells and NK cells expressing Th1/Tc1/Type 1 (IFNγ, TNFα, IL-2), Th17/Tc17/Type 17 (IL-17A, IL-17F, IL-22) cytokines and cytotoxic (perforin [PFN], granzyme [GZE] B, CD107a) markers in LNTB+ and LNTB- individuals are not known. Thus, we have studied the unstimulated (UNS) and mycobacterial antigen-induced frequencies of CD4+, CD8+ T and NK cells expressing Th1, Th17 cytokines and cytotoxic markers using flow cytometry. The frequencies of CD4+, CD8+ T and NK cells expressing cytokines and cytotoxic markers were not significantly different between LNTB+ and LNTB- individuals in UNS condition. In contrast, upon Mtb antigen stimulation, LNTB+ individuals are associated with significantly increased frequencies of CD4+ T cells (PPD [IFNγ, TNFα], ESAT-6 PP [IFNγ, TNFα], CFP-10 PP [IFNγ, TNFα, IL-2]), CD8+ T cells (PPD [IFNγ], ESAT-6 PP [IFNγ], CFP-10 PP [TNFα]) and NK cells (PPD [IFNγ, TNFα], ESAT-6 PP [IFNγ, TNFα], CFP-10 PP [TNFα]) expressing Th1/Tc1/Type 1, but not Th17/Tc17/Type 17 cytokines and cytotoxic markers compared to LNTB- individuals. LNTB+ individuals did not show any significant alterations in the frequencies of CD4+, CD8+ T cells and NK cells expressing cytokines and cytotoxic markers compared to LNTB- individuals upon HIV Gag PP and P/I antigen stimulation. Increased frequencies of CD4+, CD8+ T and NK cells expressing Th1/Tc1/Type 1 cytokines among the LNTB+ group indicates that the presence of mycobacteria plays a dominant role in the activation of key correlates of immune protection or induces higher immunopathology.
MeSH term(s)	Biomarkers ; CD4-Positive T-Lymphocytes ; CD8-Positive T-Lymphocytes ; Cytokines ; Humans ; Interleukin-2 ; Killer Cells, Natural ; Mycobacterium ; Th1 Cells ; Tuberculin ; Tuberculosis, Lymph Node ; Tumor Necrosis Factor-alpha
Chemical Substances	Biomarkers ; Cytokines ; Interleukin-2 ; Tuberculin ; Tumor Necrosis Factor-alpha
Language	English
Publishing date	2022-05-26
Publishing country	United States
Document type	Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0269109
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Article ; Online: Impact of Strongyloides stercoralis infection on complement activation in Type 2 diabetes mellitus: Insights from a clinical and anthelmintic intervention study.

Rajamanickam, Anuradha / Dasan, Bindu / Munisankar, Saravanan / Nott, Sujatha / Menon, Pradeep A / Ahamed Shaik, Fayaz / Chinnaiyan, Ponnuraja / Nutman, Thomas B / Babu, Subash

PLoS neglected tropical diseases

2024 Volume 18, Issue 4, Page(s) e0012048

Abstract: Background: Numerous studies indicate a potential protective role of helminths in diabetes mellitus (DM) progression. The complement system, vital for host defense, plays a crucial role in tissue homeostasis and immune surveillance. Dysregulated ... ...

Abstract	Background: Numerous studies indicate a potential protective role of helminths in diabetes mellitus (DM) progression. The complement system, vital for host defense, plays a crucial role in tissue homeostasis and immune surveillance. Dysregulated complement activation is implicated in diabetic complications. We aimed to investigate the influence of the helminth, Strongyloides stercoralis (Ss) on complement activation in individuals with type 2 DM (T2D). Methodology: We assessed circulating levels of complement proteins (C1q, C2, C3, C4, C4b, C5, C5a, and MBL (Lectin)) and their regulatory components (Factor B, Factor D, Factor H, and Factor I) in individuals with T2D with (n = 60) or without concomitant Ss infection (n = 58). Additionally, we evaluated the impact of anthelmintic therapy on these parameters after 6 months in Ss-infected individuals (n = 60). Results: Ss+DM+ individuals demonstrated reduced levels of complement proteins (C1q, C4b, MBL (Lectin), C3, C5a, and C3b/iC3b) and complement regulatory proteins (Factor B and Factor D) compared to Ss-DM+ individuals. Following anthelmintic therapy, there was a partial reversal of these levels in Ss+DM+ individuals. Conclusion: Our findings indicate that Ss infection reduces complement activation, potentially mitigating inflammatory processes in individuals with T2D. The study underscores the complex interplay between helminth infections, complement regulation, and diabetes mellitus, offering insights into potential therapeutic avenues.
MeSH term(s)	Animals ; Humans ; Strongyloides stercoralis ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/drug therapy ; Complement Factor B ; Complement Factor D/therapeutic use ; Complement C1q ; Strongyloidiasis/complications ; Strongyloidiasis/drug therapy ; Complement Activation ; Anthelmintics/therapeutic use ; Helminths ; Lectins
Chemical Substances	Complement Factor B (EC 3.4.21.47) ; Complement Factor D (EC 3.4.21.46) ; Complement C1q (80295-33-6) ; Anthelmintics ; Lectins
Language	English
Publishing date	2024-04-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	2429704-5
ISSN	1935-2735 ; 1935-2735
ISSN (online)	1935-2735
ISSN	1935-2735
DOI	10.1371/journal.pntd.0012048
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Article ; Online: Systemic Levels of Pro-Inflammatory Cytokines and Post-Treatment Modulation in Tuberculous Lymphadenitis.

Kathamuthu, Gokul Raj / Moideen, Kadar / Sridhar, Rathinam / Baskaran, Dhanaraj / Babu, Subash

Tropical medicine and infectious disease

2023 Volume 8, Issue 3

Abstract: Pro-inflammatory cytokines are potent stimulators of inflammation and immunity and markers of infection severity and bacteriological burden in pulmonary tuberculosis (PTB). Interferons could have both host-protective and detrimental effects on ... ...

Abstract	Pro-inflammatory cytokines are potent stimulators of inflammation and immunity and markers of infection severity and bacteriological burden in pulmonary tuberculosis (PTB). Interferons could have both host-protective and detrimental effects on tuberculosis disease. However, their role has not been studied in tuberculous lymphadenitis (TBL). Thus, we evaluated the systemic pro-inflammatory (interleukin (IL)-12, IL-23, interferon (IFN)α, and IFNβ) cytokine levels in TBL, latent tuberculosis (LTBI), and healthy control (HC) individuals. In addition, we also measured the baseline (BL) and post-treatment (PT) systemic levels in TBL individuals. We demonstrate that TBL individuals are characterized by increased pro-inflammatory (IL-12, IL-23, IFNα, IFNβ) cytokines when compared to LTBI and HC individuals. We also show that after anti-tuberculosis treatment (ATT) completion, the systemic levels of pro-inflammatory cytokines were significantly modulated in TBL individuals. A receiver operating characteristic (ROC) analysis revealed IL-23, IFNα, and IFNβ significantly discriminated TBL disease from LTBI and/or HC individuals. Hence, our study demonstrates the altered systemic levels of pro-inflammatory cytokines and their reversal after ATT, suggesting that they are markers of disease pathogenesis/severity and altered immune regulation in TBL disease.
Language	English
Publishing date	2023-02-27
Publishing country	Switzerland
Document type	Journal Article
ISSN	2414-6366
ISSN (online)	2414-6366
DOI	10.3390/tropicalmed8030150
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Article ; Online: Effect of prediabetes on tuberculosis treatment outcomes: A study from South India.

Viswanathan, Vijay / Devarajan, Arutselvi / Kumpatla, Satyavani / Dhanasekaran, Mythili / Babu, Subash / Kornfeld, Hardy

Diabetes & metabolic syndrome

2023 Volume 17, Issue 7, Page(s) 102801

Abstract: Background and aims: The aim was to assess the effect of prediabetes on tuberculosis(TB) treatment outcomes.: Methods: This is a prospective observational cohort study of 569 eligible new smear positive cases screened for DM between 2014 and 2018 in ... ...

Abstract	Background and aims: The aim was to assess the effect of prediabetes on tuberculosis(TB) treatment outcomes. Methods: This is a prospective observational cohort study of 569 eligible new smear positive cases screened for DM between 2014 and 2018 in TB units in North Chennai, South India. Based on study criteria, a total of 187 subjects were included and categorised into two groups: TB with normoglycaemia (groupI) (HbA1c<5.7%) and TB with prediabetes (group II) (HbA1c = 5.7-6.4%) and followed them at 3 Results: Total cure rate was 72.7% with no significant difference between the groups. Higher proportion of deaths occurred in group II (6.3%) compared to group I (1.3%) (p = 0.09). At the end of intensive phase of directly observed therapy (DOTS) treatment, about 23.8% were observed to have positive sputum smear in group II compared to 8.6% in group I(p = 0.019). The estimated relative risk to remain as sputum smear positive among people with prediabetes at the end of intensive phase was 3.0(95% CI: 1.2-7.6). There was a significant association found with HbA1c at enrollment and unfavourable TB treatment outcomes (β = 1.38, [odds ratio (95% CI) 3.98(1.65-9.64); p = 0.007]. Conclusion: Death rate was high and there was a delay in sputum conversion among TB patients with prediabetes at the end of the intensive phase of TB treatment. HbA1c at the time of diagnosis of prediabetes was significantly associated with unfavourable TB treatment outcomes.
MeSH term(s)	Humans ; Antitubercular Agents/therapeutic use ; Tuberculosis, Pulmonary ; Cohort Studies ; Prediabetic State/drug therapy ; Prediabetic State/epidemiology ; Glycated Hemoglobin ; India/epidemiology ; Tuberculosis/complications ; Tuberculosis/drug therapy ; Tuberculosis/epidemiology
Chemical Substances	Antitubercular Agents ; Glycated Hemoglobin
Language	English
Publishing date	2023-06-08
Publishing country	Netherlands
Document type	Observational Study ; Journal Article
ZDB-ID	2273766-2
ISSN	1878-0334 ; 1871-4021
ISSN (online)	1878-0334
ISSN	1871-4021
DOI	10.1016/j.dsx.2023.102801
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Article: Multi-Dimensionality Immunophenotyping Analyses of MAIT Cells Expressing Th1/Th17 Cytokines and Cytotoxic Markers in Latent Tuberculosis Diabetes Comorbidity

Kathamuthu, Gokul Raj / Pavan Kumar, Nathella / Moideen, Kadar / Dolla, Chandrakumar / Kumaran, Paul / Babu, Subash

Pathogens. 2022 Jan. 12, v. 11, no. 1

2022

Abstract: Mucosal-associated invariant T (MAIT) cells are innate like, and play a major role in restricting disease caused by Mycobacterium tuberculosis (Mtb) disease before the activation of antigen-specific T cells. Additionally, the potential link and ... ...

Abstract	Mucosal-associated invariant T (MAIT) cells are innate like, and play a major role in restricting disease caused by Mycobacterium tuberculosis (Mtb) disease before the activation of antigen-specific T cells. Additionally, the potential link and synergistic function between diabetes mellitus (DM) and tuberculosis (TB) has been recognized for a long time. However, the role of MAIT cells in latent TB (LTB) DM or pre-DM (PDM) and non-DM (NDM) comorbidities is not known. Hence, we examined the frequencies (represented as geometric means, GM) of unstimulated (UNS), mycobacterial (purified protein derivative (PPD) and whole-cell lysate (WCL)), and positive control (phorbol myristate acetate (P)/ionomycin (I)) antigen stimulated MAIT cells expressing Th1 (IFNγ, TNFα, and IL-2), Th17 (IL-17A, IL-17F, and IL-22), and cytotoxic (perforin (PFN), granzyme (GZE B), and granulysin (GNLSN)) markers in LTB comorbidities by uniform manifold approximation (UMAP) and flow cytometry. We also performed a correlation analysis of Th1/Th17 cytokines and cytotoxic markers with HbA1c, TST, and BMI, and diverse hematological and biochemical parameters. The UMAP analysis demonstrated that the percentage of MAIT cells was higher; T helper (Th)1 cytokine and cytotoxic (PFN) markers expressions were different in LTB-DM and PDM individuals in comparison to the LTB-NDM group on UMAP. Similarly, no significant difference was observed in the geometric means (GM) of MAIT cells expressing Th1, Th17, and cytotoxic markers between the study population under UNS conditions. In mycobacterial antigen stimulation, the GM of Th1 (IFNγ (PPD and WCL), TNFα (PPD and WCL), and IL-2 (PPD)), and Th17 (IL-17A, IL-17F, and IL-22 (PPD and/or WCL)) cytokines were significantly elevated and cytotoxic markers (PFN, GZE B, and GNLSN (PPD and WCL)) were significantly reduced in the LTB-DM and/or PDM group compared to the LTB-NDM group. Some of the Th1/Th17 cytokines and cytotoxic markers were significantly correlated with the parameters analyzed. Overall, we found that different Th1 cytokines and cytotoxic marker population clusters and increased Th1 and Th17 (IL-17A, IL-22) cytokines and diminished cytotoxic markers expressing MAIT cells are associated with LTB-PDM and DM comorbidities.
Keywords	CD4-positive T-lymphocytes ; Mycobacterium tuberculosis ; acetates ; antigens ; comorbidity ; cytotoxicity ; diabetes mellitus ; flow cytometry ; geometry ; immunophenotyping ; interleukin-17 ; interleukin-2 ; tuberculosis
Language	English
Dates of publication	2022-0112
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2695572-6
ISSN	2076-0817
ISSN	2076-0817
DOI	10.3390/pathogens11010087
Database	NAL-Catalogue (AGRICOLA)

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Article: Modulatory effect of filarial infection on the systemic hormone levels in subjects with metabolic syndrome (DM-LF5).

Sibi, Joy Manohar / Mohan, Viswanathan / Deepa, Mohan / Babu, Subash / Aravindhan, Vivekanandhan

Frontiers in endocrinology

2022 Volume 13, Page(s) 1011942

Abstract: Aim: Metabolic syndrome (MS) refers to a group of co-morbidities which include central obesity, hypertension, hyperglycemia and dyslipidemia. Previously, we reported that childhood lymphatic filariasis (LF) confers significant protection against type-1 ... ...

Abstract	Aim: Metabolic syndrome (MS) refers to a group of co-morbidities which include central obesity, hypertension, hyperglycemia and dyslipidemia. Previously, we reported that childhood lymphatic filariasis (LF) confers significant protection against type-1 and type-2 forms of diabetes, by means of immunomodulation. In the present study, we studied the effect of LF on endocrine dysfunction in MS and Non-MS patients in baseline and after 10 years of follow-up. Methods: We quantified the serum levels of pancreatic hormones (insulin and glucagon), incretins (Ghrelin, GIP and GLP-1) and adipokines (leptin, adiponectin, adipsin, visfatin, PAI-1 and resistin) by multiplex bead array system. Results: MS (both LF- and LF+) subjects had increased insulin levels compared to NMS (both LF- and LF+) subjects. MS-LF+ subjects had significantly increased levels of glucagon, ghrelin, GIP and GLP-1 and decreased levels of adipsin, compared to MS-LF- subjects. Interestingly this effect was short-lived and was not seen in the follow-up samples. Conclusion: Overall, LF infection might confer limited short-term beneficial effects against MS, by means of modulating the incretin levels,either directly or indirectly.
MeSH term(s)	Humans ; Child ; Metabolic Syndrome ; Glucagon ; Insulin
Chemical Substances	Glucagon (9007-92-5) ; Insulin
Language	English
Publishing date	2022-11-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2022.1011942
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Article ; Online: <i>Strongyloidiasis stercoralis</i> coinfection is associated with altered iron status biomarkers in tuberculous lymphadenitis.

Kathamuthu, Gokul Raj / Rajamanickam, Anuradha / Sridhar, Rathinam / Baskaran, Dhanaraj / Babu, Subash

Frontiers in immunology

2022 Volume 13, Page(s) 999614

Abstract: Soil-transmitted helminth [mainly ... Strongyloidiasis stercoralis ... (Ss)] and tuberculous lymphadenitis (TBL) coinfection in humans is a significant public health problem. We have previously shown that TBL+Ss+ coinfection significantly alters diverse ... ...

Abstract	Soil-transmitted helminth [mainly Strongyloidiasis stercoralis (Ss)] and tuberculous lymphadenitis (TBL) coinfection in humans is a significant public health problem. We have previously shown that TBL+Ss+ coinfection significantly alters diverse cytokine, matrix metalloproteinase, and tissue inhibitors of metalloproteinase profiles. However, no data is available to understand the influence of Ss coinfection in TBL disease with respect to iron status biomarkers. Hence, we have studied the effect of Ss coinfection on the circulating levels of iron status (ferritin, transferrin [TF], apotransferrin [ApoT], hepcidin, hemopexin) biomarkers in TBL disease. Our results show that TBL+Ss+ and/or TBL+Ss- individuals are associated with significantly altered biochemical and hematological (red blood cell (RBC) counts, hemoglobin (Hb), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) were decreased, and platelets were increased) parameters compared to TBL-Ss+ individuals. Our results also show that TBL+Ss+ coinfection is associated with diminished circulating levels of ferritin, ApoT, hepcidin, and hemopexin compared to TBL+Ss- individuals. TBL+Ss+ and TBL+Ss- groups are associated with altered iron status biomarkers (decreased ferritin [TBL+Ss+ alone] and increased TF, ApoT, hepcidin and hemopexin [TBL+Ss- alone]) compared to TBL-Ss+ group. The heat map expression profile and principal component analysis (PCA) analysis of iron status biomarkers were significantly altered in TBL+Ss+ compared to TBL+Ss- and/or TBL-Ss+ individuals. A significant correlation (positive/negative) was obtained among the biochemical and hematological parameters (white blood cells (WBC)/ferritin, TF, and hepcidin, mean corpuscular hemoglobin concentration (MCHC)/ferritin and hemopexin) with iron status biomarkers. Finally, receiver operating characteristic (ROC) analysis revealed that hemopexin was significantly associated with greater specificity and sensitivity in discriminating TBL+Ss+ and TBL+Ss- coinfected individuals. Thus, our data conclude that Ss coinfection is associated with altered iron status biomarkers indicating that coinfection might alter the host-Mtb interface and could influence the disease pathogenesis.
MeSH term(s)	Humans ; Strongyloidiasis/complications ; Strongyloidiasis/diagnosis ; Iron/metabolism ; Hepcidins/metabolism ; Coinfection ; Hemopexin/metabolism ; Tuberculosis, Lymph Node ; Ferritins ; Biomarkers
Chemical Substances	Iron (E1UOL152H7) ; Hepcidins ; Hemopexin (9013-71-2) ; Ferritins (9007-73-2) ; Biomarkers
Language	English
Publishing date	2022-10-20
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.999614
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Article: Multi-Dimensionality Immunophenotyping Analyses of MAIT Cells Expressing Th1/Th17 Cytokines and Cytotoxic Markers in Latent Tuberculosis Diabetes Comorbidity.

Kathamuthu, Gokul Raj / Pavan Kumar, Nathella / Moideen, Kadar / Dolla, Chandrakumar / Kumaran, Paul / Babu, Subash

Pathogens (Basel, Switzerland)

2022 Volume 11, Issue 1

Abstract: Mucosal-associated invariant T (MAIT) cells are innate like, and play a major role in restricting disease caused ... ...

Abstract	Mucosal-associated invariant T (MAIT) cells are innate like, and play a major role in restricting disease caused by
Language	English
Publishing date	2022-01-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2695572-6
ISSN	2076-0817
ISSN	2076-0817
DOI	10.3390/pathogens11010087
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