9 research outputs found
Plasma Vitamin D levels in correlation with circulatory proteins could be a potential biomarker tool for pulmonary tuberculosis and treatment monitoring
Background: Tuberculosis (TB), a life-threatening immune challenging disease to the global human community
has to be diagnosed earlier and eliminated in the upcoming era. Vitamin D, a fat-soluble micronutrient, mainly
from epidermal cells of the skin and a few dietary sources, is associated with the immune system in various
disease management. Therefore, a better understanding of vitamin D metabolism and immune function in
tuberculosis should be studied for the consideration of biomarkers.
Methods: The study consist of Pulmonary Tuberculosis (PTB) patients (n = 32) at two-time points: Baseline (PTB
BL) and after 6 months of anti-TB treatment (ATT) (PTB PT), latently Mtb infected (IFNĪ³ + ) group (n = 32) and a
non-LTB healthy control (IFNĪ³-) group (n = 32). Vitamin D levels were measured using High-performance liquid
chromatography (HPLC). The cytokine data from the same participants assayed by ELISA from our earlier inļæ½vestigations were used to correlate it with serum Vitamin D levels.
Results: The assayed serum Vitamin D levels between the groups showed significantly lowered levels in PTB BL
when compared with IFNĪ³ + and IFNĪ³- groups. And, the Vitamin D levels in the PTB group after ATT were
significantly lower than the baseline levels. The Vitamin D data were compared with pro- and anti-inflammatory
cytokines and adipokines levels by performing a principal component regression analysis. Based on the PC scores,
the study group showed distinct clusters for the TB group and control group. And, the correlation analysis beļæ½tween the study group and immunological indices showed significant correlations. Vitamin D significantly
correlated with IFNĪ³, TNFĪ±, IL17A, IL-4 and Resistin in the TB group, whereas IL-6 and G-CSF in the control
group.
Conclusion: The baseline measurement of Vitamin D levels was significantly decreased in the PTB group when
compared with IFNĪ³ + and IFNĪ³- groups showing the importance of Vitamin D as a preventive factor against the
TB disease progression. The six-month post-treatment of TB showed a further decrease in Vitamin D levels in
PTB. The significantly correlated immunological indices with Vitamin D levels are the biomarker profile that
could predict TB
Latent tuberculosis co-infection is associated with heightened levels of humoral, cytokine and acute phase responses in seropositive SARS-CoV-2 infection
OBJECTIVES: : Latent Tuberculosis infection (LTBI) is postulated to modulate immune responses and alter disease severity in SARS-CoV-2 co-infection. However, no data exist on the effect of LTBI on the immune responses in SARS-CoV-2 co-infected individuals. METHODS: : We examined the SARS-CoV-2 specific antibody responses, plasma cytokines, chemokines, acute phase proteins and growth factor levels in LTBI positive and negative individuals with SARS-CoV-2 infection. RESULTS: : Our results demonstrated that individuals with LTBI (LTBI+) and seropositive for SARS-CoV-2 infection were associated with elevated SARS-CoV-2 specific IgM, IgG and IgA antibodies, as well as enhanced neutralization activity compared to those negative for LTBI (LTBI-) individuals. Our results also demonstrate that LTBI+ individuals exhibited significantly higher plasma levels of IFNĪ³, IL-2, TNFĪ±, IL-1Ī±, IL-1Ī², IL-6, IL-12, IL-15, IL-17, IL-3, GM-CSF, IL-10, IL-25, IL-33, CCL3 and CXCL10 compared to LTBI- individuals. Finally, our results show that LTBI+ individuals exhibit significantly higher levels of C-reactive protein, alpha-2 macroglobulin, VEGF and TGFĪ± compared to LTBI- individuals. CONCLUSIONS: : Thus, our data clearly demonstrates that LTBI+ individuals seropositive for SARS-CoV2 infection exhibit heightened levels of humoral, cytokine and acute phase responses compared to LTBI- individuals. Thus, LTBI is associated with modulation of antibody and cytokine responses as well as systemic inflammation in individuals seropositive for SARS-CoV2 infection
BCG vaccination induces enhanced frequencies of dendritic cells and altered plasma levels of type I and type III interferons in elderly individuals
OBJECTIVE: : BCG can improve the response to vaccines directed against viral infections and also BCG vaccination reduces all-cause mortality, most likely by protection against unrelated infections. However, the effect of BCG vaccination on the dendritic cells (DC) subsets is not well characterized. METHODS: : We investigated the impact of BCG vaccination on the frequencies of DC subsets and type I and III interferons (IFNs) using whole blood and plasma samples in a group of elderly individuals (age 60-80 years) at one month post vaccination as part of our clinical study to examine the effect of BCG on COVID-19. RESULTS: : Our results demonstrate that BCG vaccination induced enhanced frequencies of plasmacytoid DC (pDC) and myeloid DC (mDC). BCG vaccination also induced diminished plasma levels of type I IFNs like IFNĪ±Ā and IFNĪ² but increased levels of type III IFNs IL-28A and IL-29. CONCLUSIONS: : Thus, BCG vaccination was associated with enhanced DC subsets as well IL-29 in elderly individuals, suggesting its ability to induce non-specific innate immune responses
BCG vaccination induces enhanced frequencies of memory T cells and altered plasma levels of common Ī³c cytokines in elderly individuals
BCG vaccination is known to induce innate immune memory, which confers protection against heterologous infections. However, the effect of BCG vaccination on the conventional adaptive immune cells subsets is not well characterized. We investigated the impact of BCG vaccination on the frequencies of T cell subsets and common gamma c (Ī³c) cytokines in a group of healthy elderly individuals (age 60ā80 years) at one month post vaccination as part of our clinical study to examine the effect of BCG on COVID-19. Our results demonstrate that BCG vaccination induced enhanced frequencies of central (p<0.0001) and effector memory (p<0.0001) CD4+ T cells and diminished frequencies of naĆÆve (p<0.0001), transitional memory (p<0.0001), stem cell memory (p = 0.0001) CD4+ T cells and regulatory T cells. In addition, BCG vaccination induced enhanced frequencies of central (p = 0.0008), effector (p<0.0001) and terminal effector memory (p<0.0001) CD8+ T cells and diminished frequencies of naĆÆve (p<0.0001), transitional memory (p<0.0001) and stem cell memory (p = 0.0034) CD8+T cells. BCG vaccination also induced enhanced plasma levels of IL-7 (p<0.0001) and IL-15 (p = 0.0020) but diminished levels of IL-2 (p = 0.0033) and IL-21 (p = 0.0020). Thus, BCG vaccination was associated with enhanced memory T cell subsets as well as memory enhancing Ī³c cytokines in elderly individuals, suggesting its ability to induce non-specific adaptive immune responses
Enhanced SARS-CoV-2-Specific CD4+ T Cell Activation and Multifunctionality in Late Convalescent COVID-19 Individuals
Background: Examination of CD4(+) T cell responses during the natural course of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection offers useful information for the improvement of vaccination strategies against this virus and the protective effect of these T cells. Methods: We characterized the SARS-CoV-2-specific CD4(+) T cell activation marker, multifunctional cytokine and cytotoxic marker expression in recovered coronavirus disease 2019 (COVID-19) individuals. Results: CD4(+) T-cell responses in late convalescent (>6 months of diagnosis) individuals are characterized by elevated frequencies of activated as well as mono, dual- and multi-functional Th1 and Th17 CD4(+) T cells in comparison to early convalescent (<1 month of diagnosis) individuals following stimulation with SARS-CoV-2-specific antigens. Similarly, the frequencies of cytotoxic marker expressing CD4(+) T cells were also enhanced in late convalescent compared to early convalescent individuals. Conclusion: Our findings from a low-to middle-income country suggest protective adaptive immune responses following natural infection of SARS-CoV-2 are elevated even at six months following initial symptoms, indicating the CD4(+) T cell mediated immune protection lasts for six months or more in natural infection
Dynamic alterations in monocyte numbers, subset frequencies and activation markers in acute and convalescent COVID-19 individuals
Monocytes are thought toĀ play an important role in host defence and pathogenesis of COVID-19. However, a comprehensive examination of monocyte numbers and function has not been performed longitudinally in acute and convalescent COVID-19. We examined the absolute counts of monocytes, the frequency of monocyte subsets, the plasma levels of monocyte activation markers using flowcytometry and ELISA in seven groups of COVID-19 individuals, classified based on days since RT-PCR confirmation of SARS-CoV2 infection. Our data shows that the absolute counts of total monocytes and the frequencies of intermediate and non-classical monocytes increases from Days 15ā30 to Days 61ā90 and plateau thereafter. In contrast, the frequency of classical monocytes decreases from Days 15ā30 till Days 121ā150. The plasma levels of sCD14, CRP, sCD163 and sTissue Factor (sTF)āall decrease from Days 15ā30 till Days 151ā180. COVID-19 patients with severe disease exhibit higher levels of monocyte counts and higher frequencies of classical monocytes and lower frequencies of intermediate and non-classical monocytes and elevated plasma levels of sCD14, CRP, sCD163 and sTF in comparison with mild disease. Thus, our study provides evidence of dynamic alterations in monocyte counts, subset frequencies and activation status in acute and convalescent COVID-19 individuals
Characterization of memory T cell subsets and common Ī³āchain cytokines in convalescent COVID-19 individuals
T cells are thought to be an important correlates of protection against SARSāCoV2 infection. However, the composition of T cell subsets in convalescent individuals of SARSāCoV2 infection has not been well studied. The authors determined the lymphocyte absolute counts, the frequency of memory T cell subsets, and the plasma levels of common Ī³āchain in 7 groups of COVIDā19 individuals, based on days since RTāPCR confirmation of SARSāCoVā2 infection. The data show that both absolute counts and frequencies of lymphocytes as well as, the frequencies of CD4(+) central and effector memory cells increased, and the frequencies of CD4(+) naĆÆve T cells, transitional memory, stem cell memory T cells, and regulatory cells decreased from Days 15ā30 to Days 61ā90 and plateaued thereafter. In addition, the frequencies of CD8(+) central memory, effector, and terminal effector memory T cells increased, and the frequencies of CD8(+) naĆÆve cells, transitional memory, and stem cell memory T cells decreased from Days 15ā30 to Days 61ā90 and plateaued thereafter. The plasma levels of ILā2, ILā7, ILā15, and ILā21ācommon Ī³c cytokines started decreasing from Days 15ā30 till Days 151ā180. Severe COVIDā19 patients exhibit decreased levels of lymphocyte counts and frequencies, higher frequencies of naĆÆve cells, regulatory T cells, lower frequencies of central memory, effector memory, and stem cell memory, and elevated plasma levels of ILā2, ILā7, ILā15, and ILā21. Finally, there was a significant correlation between memory T cell subsets and common Ī³c cytokines. Thus, the study provides evidence of alterations in lymphocyte counts, memory T cell subset frequencies, and common Ī³āchain cytokines in convalescent COVIDā19 individuals
Recovery of Memory B-cell Subsets and Persistence of Antibodies in Convalescent COVID-19 Patients
Unique cellular immune signatures of multisystem inflammatory syndrome in children
The clinical presentation of MIS-C overlaps with other infectious/non-infectious diseases such as acute COVID-19, Kawasaki disease, acute dengue, enteric fever, and systemic lupus erythematosus. We examined the ex-vivo cellular parameters with the aim of distinguishing MIS-C from other syndromes with overlapping clinical presentations. MIS-C children differed from children with non-MIS-C conditions by having increased numbers of naĆÆve CD8(+) T cells, naĆÆve, immature and atypical memory B cells and diminished numbers of transitional memory, stem cell memory, central and effector memory CD4(+) and CD8(+) T cells, classical, activated memory B and plasma cells and monocyte (intermediate and non-classical) and dendritic cell (plasmacytoid and myeloid) subsets. All of the above alterations were significantly reversed at 6ā9 months post-recovery in MIS-C. Thus, MIS-C is characterized by a distinct cellular signature that distinguishes it from other syndromes with overlapping clinical presentations. Trial Registration: ClinicalTrials.gov clinicaltrial.gov. No: NCT04844242