Role of neutrophils in tuberculosis: A bird's eye view.

Neutrophils are innate immune cells implicated in the process of killing early during infection. Once the mycobacteria enter the human system, neutrophils sense and engulf them. By secreting bactericidal enzymes and α-defensins like human neutrophil peptides loaded in their granule armory, neutrophils kill the pathogen.

Neutrophil CD64, TLR2 and TLR4 expression increases but phagocytic potential decreases during tuberculosis.

During initial stages of pathogen recognition during tuberculosis infection, neutrophils provide significant immune resistance. This is exhibited by phagocytosis of the pathogen, apoptosis, activation of downstream immune responses, etc. As pathogen recognition by neutrophil cell surface receptor and phagocytosis marks the initial step in any immune response, knowledge on receptor modulations during tuberculosis infection will augment drug designing strategies for the disease.

Proteomics Analysis of Three Different Strains of Mycobacterium tuberculosis under In vitro Hypoxia and Evaluation of Hypoxia Associated Antigen's Specific Memory T Cells in Healthy Household Contacts.

In vitro mimicking conditions are thought to reflect the environment experienced by Mycobacterium tuberculosis inside the host granuloma. The majority of in vitro dormancy experimental models use laboratory-adapted strains H37Rv or Erdman instead of prevalent clinical strains involved during disease outbreaks. Thus, we included the most prevalent clinical strains (S7 and S10) of M.

TLR stimulation of human neutrophils lead to increased release of MCP-1, MIP-1α, IL-1β, IL-8 and TNF during tuberculosis.

Neutrophils inform and shape immune responses. Toll-like receptors (TLRs) play an essential part in the perception of microbes and shape the complex host responses that occur during infection. The TLRs present on neutrophils play an indispensable role in neutrophil mediated pathogen recognition and elimination.

Mycobacterium tuberculosis strains modify granular enzyme secretion and apoptosis of human neutrophils.

Mycobacterium tuberculosis has evolved to employ multiple strategies to avoid an efficient host immune response. Accordingly, enzymes are important antimycobacterial elements and apoptosis decides the fate of any cell. Hence, we carried out this study to discern the amplitude of two clinical stains (S7 & S10) and a laboratory strain (H37Rv) of M.

The influence of reduced oxygen availability on gene expression in laboratory (H37Rv) and clinical strains (S7 and S10) of Mycobacterium tuberculosis.

Mycobacterium tuberculosis has the ability to persist within the host in a dormant stage. One important condition believed to contribute to dormancy is reduced access to oxygen known as hypoxia. However, the response of M.

Neutrophils from pulmonary tuberculosis patients show augmented levels of chemokines MIP-1α, IL-8 and MCP-1 which further increase upon in vitro infection with mycobacterial strains.

Neutrophils being innate cells initiate the immune defence against mycobacteria by sending signals to other immune cells. Chemokines being the vital link in signaling processes, it is of interest to study their secretion by neutrophils as a response to tuberculosis infection. The levels of various chemokines (MIP-1α, MCP-1, IL-8 and IP-10) and chemokine receptors (CXCR1, CXCR2 and CCR1) in neutrophils from healthy individuals and pulmonary tuberculosis patients were studied following infection with Mycobacterium tuberculosis strains (clinical--S7 and S10 and laboratory--H37Rv).

Mycobacterium tuberculosis H37Rv is more effective compared to vaccine strains in modulating neutrophil functions: an in vitro study.

Neutrophils are the primary cells contributing to initial defense against mycobacteria. Yet, little is known about the potential of various mycobacterial strains to stimulate neutrophils. This study was focused to compare the differential capacity of vaccine strains, Mycobacterium bovis bacillus Calmette-Guerin (BCG) and Mycobacterium indicus pranii (Mw), and laboratory strain H37Rv to activate and enhance neutrophil functions.

Comparison of localized versus systemic levels of Matrix metalloproteinases (MMPs), its tissue inhibitors (TIMPs) and cytokines in tuberculous and non-tuberculous pleuritis patients.

The interaction of Matrix metalloproteinases (MMPs), its tissue inhibitors (TIMPs) and pro-inflammatory cytokines in response to Mycobacterium tuberculosis (MTB) infection is important to understand the immune response at the site of infection. We compared the levels of MMPs, TIMPs and cytokines in plasma (BL) and pleural fluid (PF) of tuberculosis (TB) and non tuberculosis (NTB) patients. Comparison between BL and PF showed significantly higher levels of MMP-1, TIMP-1 and -3 in TB PF; of MMP-7, -8, -9 in BL of both groups.

Phenotypic modulation in Mycobacterium tuberculosis infected neutrophil during tuberculosis.

Background & Objective: Polymorphonuclear leucocytes (PMN) or neutrophils infiltrate to the inflammatory sites and phagocytose mycobacteria thereby inhibiting the bacillary spread initially until the accumulated macrophages get activated. The present study was carried out to highlight the interaction of neutrophils with the two clinical isolates (S7 and S10) of Mycobacterium tuberculosis and the subsequent morphological changes.

Methods: Dextran purified neutrophils from normal and TB patients infected with M.

Leptin response in patients with tuberculous pleuritis.

Background & Objectives: Tuberculous pleuritis is used as a model to understand the protective immune response in tuberculosis. It is predominated by Th1 response at the site of infection, where a possible role for the leptin, a known enhancer of Th1 response, could be speculated. Hence, we investigated leptin levels in pleural effusions in patients with both tuberculous (TP) and non-tuberculous (NTP) pleural effusion.

Differential upregulation of chemokine receptors on CD56 NK cells and their transmigration to the site of infection in tuberculous pleurisy.

Chemokines and their receptors orchestrate leukocyte recruitment and confer immunity during Mycobacterium tuberculosis infection. The immunoregulatory and cytotoxic activities of natural killer (NK) cells are essential at the site of infection during tuberculous pleurisy. The frequency, subtypes, and expression of phenotype markers and chemokine receptors on NK cells were assessed by flow cytometry in tuberculous (TB) and nontuberculous (NTB) pleural fluid (PF).

Augmented chemokine levels and chemokine receptor expression on immune cells during pulmonary tuberculosis.

The systemic changes in immune mediators such as cytokine and chemokines, and their synchronized interaction that regulates the cell trafficking during Mycobacterium tuberculosis (M. tuberculosis) infection, were studied. Cytokines and chemokines were evaluated by cytometric bead array (CBA) and enzyme-linked immunosorbent assay (ELISA) in 34 pulmonary tuberculosis (PTB) patients and 30 healthy subjects.

Comparative evaluation of cytokines, T-cell apoptosis, and costimulatory molecule expression in tuberculous and nontuberculous pleurisy.

In this study, we compared several immune parameters in tuberculosis (TB) and nontuberculosis (NTB) pleurisy to gain an understanding of the mechanism behind enhanced Th1 apoptosis that occurs at sites of active Myobacterium tuberculosis (M. tuberculosis) infection. An initial evaluation of the accumulated cytokines in pleural fluid (PF) demonstrated that both TB and NTB pleurisy were associated with prointflammatory cytokines, while only TB pleurisy had augmented expression of interferon (IFN)-gamma and soluble Fas ligand (sFASL).

Impaired phenotype and function of monocyte derived dendritic cells in pulmonary tuberculosis.

Pulmonary tuberculosis (PTB) is often associated with impaired immunological functions. Blood monocytes, which can differentiate into dendritic cells upon cytokine stimulation, play a central role in adequate immune reactivity. Here, we investigated the morphologic, phenotypic and functional characteristics of in vitro-generated monocyte derived dendritic cells (MoDC) from PTB patients in comparison with healthy subjects.

Differential migration of human monocyte-derived dendritic cells after infection with prevalent clinical strains of Mycobacterium tuberculosis.

Dendritic cells (DCs) play a key role in the host immune response to infections. Mycobacterium tuberculosis (MTB) can inhibit the maturation of DCs and impair their ability to stimulate T cell proliferation. Here, we assessed in vitro migratory behavior of human monocyte-derived DCs (MoDC) when infected with various MTB strains (H37Rv and prevalent clinical strains S7 and S10 from South India).

Diagnostic utility of interferon-gamma-induced protein of 10 kDa (IP-10) in tuberculous pleurisy.

Tuberculous pleuritis (TP) is characterized by predominant Th1 immune response. We observed significantly high levels of interferon gamma (IFN-gamma) and chemokines such as IP-10, monokine induced by IFN-gamma (MIG), interleukin 8 (IL-8), monocyte chemotactic protein (MCP)-1, and macrophage inflammatory protein (MIP)-1alpha in tuberculous pleural effusions. In the current study, we evaluated the diagnostic utility of IFN-gamma-dependent chemokine especially IP-10.

Expression of co-stimulatory molecules B7.1 & B7.2 on macrophages infected with various strains of Mycobacterium tuberculosis & its influence on T-cell apoptosis.

Background & Objective: Activation of T cells is mediated through two critical signals provided by activated macrophages. The first signal is triggered when T cell receptor (TCR) binds to the major histocompatibility antigen (MHC/Ag) complex. The second signal is the interaction of co-stimulatory molecules with their respective ligands on T cells for their activation and proliferation.

Infection with prevalent clinical strains of Mycobacterium tuberculosis leads to differential maturation of monocyte derived dendritic cells.

The link between innate and adaptive host immune response to Mycobacterium tuberculosis (M.tb) is driven by dendritic cells (DC). In this study, we examined the ability of prevalent clinical strains from south India (S7, S10) and laboratory strain H37Rv (Rv) to induce maturation of monocyte derived dendritic cells (MoDC).

TLR2 and TLR4 expression on the immune cells of tuberculous pleural fluid.

Toll-like receptors (TLRs) play an important role in mediating the down stream signaling of immune response in tuberculosis. The predominance of Th1 response in tuberculous pleurisy prompted us to study the expression profiles of TLR2 and TLR4 on different immune cells and on subsets of T cells obtained from the site of infection. Our results showed that TLR2 was up-regulated on the monocytes from pleural fluid indicating a prominent role for this receptor in anti-tuberculous immunity.

Expression of CXC and CC type of chemokines and its receptors in tuberculous and non-tuberculous effusions.

Chemokines mediate their biological functions by transmigration of various immune cells to the site of infection. Tuberculous pleurisy provides an effective model to study the role of chemokines in the recruitment of immune cells to the pleura. Our aim was to understand the cumulative effect of chemokines (IP-10, MIG, IL-8, MCP-1, MIP-1alpha and RANTES) and its receptors (CXCR2, CXCR3, CCR1, CCR2, CCR5 and CCR7) in the recruitment of CD4(+) T cells obtained from blood (BL) and pleural fluid (PF) of tuberculous (TB) and non-tuberculous (NTB) patients.

A correlation between phagocytosis and apoptosis in THP-1 cells infected with prevalent strains of Mycobacterium tuberculosis.

The innate ability of infected macrophages to undergo programmed cell death (apoptosis) and curtail the infection is crucial for the host defense. Although phagocytosis and intracellular killing mechanisms leading to apoptosis in macrophages are highly effective in eliminating the infecting tuberculous bacilli, some Mycobacterium tuberculosis(Mtb) strains have evolved strategies to inhibit this microbicidal function and make use of macrophage for its successful and prolonged survival. Two clinical strains of Mtb (S7 and S10) found to be prevalent and primitive, based on molecular epidemiological studies, were used to study the magnitude in induction of apoptosis in THP-1 cells at various time points of infection and to correlate it with phagocytosis.

Th2-type immune response observed in healthy individuals to sonicate antigen prepared from the most prevalent Mycobacterium tuberculosis strain with single copy of IS6110.

Different Mycobacterium tuberculosis strains operate different immune evasion strategies for their survival in the host. This mainly depends on the virulence of the strain and the host immune responses. The most virulent strains are actively involved in the transmission, widely spread in the community and induce differential immune responses.

Impact of tuberculosis on serum leptin levels in patients with HIV infection.

Aim: Tuberculosis (TB) and human immunodeficiency virus (HIV) are classical wasting diseases accompanied by immunosuppression. As leptin is involved in the weight regulation and cellular immunity, we investigated the role of leptin levels in the co-infection of HIV and TB (HIV-TB).

Methods: The study group consists of the patients with asymptomatic HIV infection (n = 20), patients with HIV-TB co-infection (n = 20) and healthy control subjects (n = 20).

Differentiation of highly prevalent IS6110 single-copy strains of Mycobacterium tuberculosis from a rural community in South India with an ongoing DOTS programme.

We have prospectively analysed the DNA fingerprinting of Mycobacterium tuberculosis strains in a rural community from high prevalence area in South India with an ongoing DOTS programme. Strains from 451 culture-positive cases, diagnosed during July 1999-December 2000, were fingerprinted initially by both IS6110 and DR probes followed by polymorphic GC-rich repeat sequences (PGRS) typing only on low-copy strains. The results were correlated with selected epidemiological and clinical data.