Acquired immune responses in the lung : their relevance to bronchiectasis

Imperial Users onl

Promotion of a down-modulated lung immune state may be a strategy by M. tuberculosis to foster active disease and persistence.

One-third of humans carry Mycobacterium tuberculosis, the etiological agent of tuberculosis (TB) where microbe/host immune response interactions result in persistence or active TB. However, immune mediators associated with human TB remain poorly defined. Through a series of comparative studies of lung immune response of TB cases at the time of diagnosis and patients with other infectious lung diseases and volunteers, we found that TB cases expressed significantly higher levels of mediators that counteract Th1-type and innate immunity critical for containment of M. tuberculosis. Despite the concomitant heightened levels of Th1-type mediators, they are likely rendered ineffectual by high levels of intracellular (e.g., SOCS) and extracellular (e.g., IL-10) immune suppressors. These modulators are a direct response to M. tuberculosis as many suppressive factors declined to the levels of controls by 30 days of anti-TB treatment while most Th1-type and innate immune mediators rose above the pre-treatment levels. Parallel laboratory studies and monitored lung alveolar macrophage effector, nitric oxide synthase-2 (being shown critical for killing M. tuberculosis), support that M. tuberculosis actively promotes down-modulatory mediators to counteract Th1-type/innate immunity as an immunopathological strategy. Our studies highlight the potential application of immune mediators as surrogate markers for TB diagnosis or treatment response

Tuberculosis and HIV: renewed challenge

HIV infection is responsible for an increased incidence of pulmonary tuberculosis (TB) in several areas of the world. In general, active TB happens as a consequence of a recently acquired exogenous infection of Mycobacterium tuberculosis or of endogenous reactivation of old infection. In some regions, besides the increase of the incidence, an important change in the dynamics of the transmission of M. tuberculosis took place. This change was more evident in closed places (hospitals, prisons, housings) where the prevalence of inmates infected by HIV is high. The infection by HIV also interferes with the diagnosis of TB, especially in patients in the advanced form of the HIV infection. In these cases, the clinical picture of TB is quite similar to other opportunistic infections . HIV seropositive patients tend to stay longer in hospitals, increasing the risk of transmission of TB or even of multidrug resistant TB (TB-MDR) to other patients, health care workers and students in teaching institutions (Alland et al. loc. cit., Frieden et al. loc. cit.). The clinical evolution of co-infected patients is diverse from immunocompetent individuals, with higher rate of adverse drugs reaction and mortality. The emphasis given in the last decades to outpatient treatment of TB should be now revised in areas with high rate of TB and AIDS, especially in great urban centers. Hospital treatment of tuberculosis patients with co-morbidities, such as AIDS, is much more common now. Should be taken into account in the elaboration of public politics the occurrence of TB in general hospitals, above all in developing countries, such as Brazil

Immunoglobulin A (IgA) and IgG Immune Responses against P-90 Antigen for Diagnosis of Pulmonary Tuberculosis and Screening for Mycobacterium tuberculosis Infection

The purpose of the present study was to evaluate the usefulness of detection of serum immunoglobulin A (IgA) and IgG antibodies directed against the mycobacterial P-90 antigen for the diagnosis of active pulmonary tuberculosis (PTB) among symptomatic individuals and for the detection of Mycobacterium tuberculosis infections among close contacts of PTB patients. Two commercially available enzyme immunoassay (EIA) kits (IgA EIA-TB [EIA-IgA] and IgG EIA-TB [EIA-IgG]; Kreatech Diagnostics) were evaluated in a blinded fashion by using stored serum samples from 268 individuals, including 69 patients with PTB, 41 patients with diseases other than tuberculosis (TB), 12 subjects with healed PTB, 39 close contacts of PTB patients, and 107 healthy volunteers. For the EIA-IgA, the sensitivity was 74% and the specificity was 68% when a cutoff determined by a receiver operator characteristic curve was used. For the EIA-IgG, the sensitivity was 69% and the specificity was 64%. The EIA-IgA was positive for 54% of healthy close contacts of PTB patients but only 8% of healthy controls without contact with a PTB patient or a prior personal history of TB (P < 0.001). The relatively low sensitivities and specificities of these serologic tests make them poor tools for the diagnosis of PTB among patients with suspected PTB. However, the relatively high prevalence of positive EIA-IgA results among healthy close contacts of PTB patients warrants further evaluation of this test with close contacts and other populations at risk for recent M. tuberculosis exposure and development of disease

Mycobacterium bovis BCG killed by extended freeze-drying reduces airway hyperresponsiveness in 2 animal models.

International audienceBACKGROUND: Live BCG administered intranasally to mice inhibits the development of ovalbumin (OVA)-induced eosinophilia and airway hyperresponsiveness (AHR). It is unacceptable to treat human subjects intranasally with live BCG. OBJECTIVE: We investigated whether BCG killed by extended freeze-drying (EFD) and subcutaneously injected has a protective effect in murine and guinea pig models of allergic airway inflammation. METHODS: Mice were OVA sensitized (days 0 and 7), treated subcutaneously (day 14) with EFD and live or heat-killed BCG, and then OVA challenged (day 42). OVA-sensitized mice (days 0 and 7) were challenged (day 14) and EFD treated (day 18) before OVA rechallenge (day 46) to demonstrate the capacity of EFD to reverse the established lung inflammation. Guinea pigs were OVA sensitized (days 0 and 14), treated intradermally (day 35) with EFD, and OVA challenged (days 90-105). RESULTS: In mice and guinea pigs EFD treatment reduced AHR. Among 3 BCG preparations, only EFD efficiently reduced AHR, eosinophilia, and the recruitment of dendritic cells to the lungs after OVA challenge. The protective effect of EFD is associated with production of the immunoregulatory cytokine IL-10. Moreover, EFD treatment did not induce toxic effects or delayed-type hypersensitivity to mycobacterial antigens; that is, it did not interfere with the diagnosis of tuberculosis. CONCLUSION: EFD administered subcutaneously inhibits the development of allergic airway inflammation and prevents AHR without inducing delayed-type hypersensitivity and side effects associated with live or heat-killed BCG

Phenotypes of lung mononuclear phagocytes in HIV seronegative tuberculosis patients: Evidence for new recruitment and cell activation

Mycobacterium tuberculosis preferentially resides in mononuclear phagocytes. The mechanisms by which mononuclear phagocytes keep M. tuberculosis in check or by which the microbe evades control to cause disease remain poorly understood. As an initial effort to delineate these mechanisms, we examined by immunostaining the phenotype of mononuclear phagocytes obtained from lungs of patients with active tuberculosis. From August 1994 to March 1995, consecutive patients who had an abnormal chest X-ray, no demostrable acid-fast bacilli in sputum specimens and required a diagnostic bronchoalveolar lavage (BAL) were enrolled. Of the 39 patients enrolled, 21 had microbiologically diagnosed tuberculosis. Thirteen of the 21 tuberculosis patients were either HIV seronegative (n = 12) or had no risk factor for HIV and constituted the tuberculosis group. For comparison, M. tuberculosis negative patients who had BAL samples taken during this time (n = 9) or normal healthy volunteers (n = 3) served as control group

Immune response during HIV and tuberculosis co-infection

The human immunodeficiency virus type 1 (HIV-1) and Mycobacterium tuberculosis, the etiologic agent of tuberculosis (TB), co-infect around 6 million people worldwide. In Rio de Janeiro, Brazil, 24% of notified AIDS cases had TB and 5 to 20% of notified TB cases are HIV-1 seropositive. Several authors have already described the deleterious association between these two microorganisms. Here, we will overview the immune response to M. tuberculosis and the effect of association with HIV-1 infection. The natural history of M. tuberculosis infection indicates that the emergence of delayed-type hypersensitivity (DTH) and presumably specific acquired resistance is associated with control of the initial infection in 95% of normal hosts; the other 5% develop progressive primary TB. In addition, 5-10% of the infected persons eventually will reactivate latent pulmonary or extrapulmonary foci several years after infection. HIV-infected individuals and AIDS patients have a remarkable susceptibility to TB, increasing 113-fold and 170-fold the risk of TB reactivation, respectively. In addition, it has been shown that TB accelerates the HIV infection and disease progression

Developments in Impact Assessment of New Diagnostic Algorithms for Tuberculosis Control

A modified presentation of the impact assessment framework is proposed that improves accessibility while continuing to provide a checklist of the evidence needed to support policy decisions on the implementation of new tools for the diagnosis of tuberculosis