Human Pulmonary Tuberculosis Research Articles

Cell proliferation and interferon-gamma response to recombinant MBP-3, NarL, MT-10.3, and 16kDa Mycobacterium tuberculosis antigens in Brazilian tuberculosis patients

Human pulmonary tuberculosis (TB) is a worldwide public health problem. In resistant individuals, control of the infection mainly requires development of a Th1 cell immune response with production of cytokines, of which interferon-gamma (IFN-gamma)plays an important role. Several antigens from Mycobacterium tuberculosis complex has been described for use in vaccine development or for diagnostic purposes, however little evaluation has been done in endemic area for TB. The proliferative and IFN-gamma human T cell immune responses, to four recombinant proteins (MBP-3, NarL, MT-10.3, 16 kDa) and PPD, of 38 Brazilian TB patients (6 untreated and 32 treated) and 67 controls (38 positive and 29 negative tuberculin skin test - TST) were compared. The highest reactivity mean rate was obtained with PPD followed by 16 kDa in TB patients. While most of the patients (87%) and controls (> 64%) respond to the PPD, 16 kDa was more specifically recognized (> 21%) although less sensitive (54%). When TB patients were divided according to treatment status, opposite to PPD, higher average level of IFN-gamma was induced by 16 kDa in untreated (505 pg/ml) compared to treated TB patients and TST+ (269.8 pg/ml x 221.6 pg/ml, respectively), although the difference was not significant. These data show that in contrast with the other recombinant proteins, the stimulatory potency of 16 kDa to induce proliferative and INF-gamma response was more effective and is more recognized by active TB untreated patients, eliciting in control individuals a more selective immune response than PPD.

Does sphingosine 1-phosphate play a protective role in the course of pulmonary tuberculosis?

Sphingosine 1-phosphate (S1P) has recently been reported to induce antimycobacterial activity in vitro and in a mouse model of in vivo Mycobacterium tuberculosis infection. However, its role in the course of pulmonary tuberculosis in humans is still not known. This study shows that S1P levels in airway surface fluid of tuberculosis (TB) patients are significantly less than those observed in non-TB control patients. Moreover, the in vitro stimulation of bronchoalveolar lavage cells coming from TB patients with S1P significantly reduces intracellular growth of endogenous mycobacterial isolates. These results show that, in the course of pulmonary TB, airway epithelial fluid-associated S1P may play a protective role in the containment of intracellular mycobacterial growth and that its decrease may represent a novel pathogenic mechanism through which M. tuberculosis favors its replication.

Intranasal Boosting with an Adenovirus-Vectored Vaccine Markedly Enhances Protection by Parenteral Mycobacterium bovis BCG Immunization against Pulmonary Tuberculosis

Parenterally administered Mycobacterium bovis BCG vaccine confers only limited immune protection from pulmonary tuberculosis in humans. There is a need for developing effective boosting vaccination strategies. We examined a heterologous prime-boost regimen utilizing BCG as a prime vaccine and our recently described adenoviral vector expressing Ag85A (AdAg85A) as a boost vaccine. Since we recently demonstrated that a single intranasal but not intramuscular immunization with AdAg85A was able to induce potent protection from pulmonary Mycobacterium tuberculosis challenge in a mouse model, we compared the protective effects of parenteral and mucosal booster immunizations following subcutaneous BCG priming. Protection by BCG prime immunization was not effectively boosted by subcutaneous BCG or intramuscular AdAg85A. In contrast, protection by BCG priming was remarkably boosted by intranasal AdAg85A. Such enhanced protection by intranasal AdAg85A was correlated to the numbers of gamma interferon-positive CD4 and CD8 T cells residing in the airway lumen of the lung. Our study demonstrates that intranasal administration of AdAg85A represents an effective way to boost immune protection by parenteral BCG vaccination.

An autosomal dominant major gene confers predisposition to pulmonary tuberculosis in adults

The molecular basis of genetic predisposition to pulmonary tuberculosis in adults remains largely elusive. Few candidate genes have consistently been implicated in tuberculosis susceptibility, and no conclusive linkage was found in two previous genome-wide screens. We report here a genome-wide linkage study in a total sample of 96 Moroccan multiplex families, including 227 siblings with microbiologically and radiologically proven pulmonary tuberculosis. A genome-wide scan conducted in half the sample (48 families) identified five regions providing suggestive evidence (logarithm of the odds [LOD] score >1.17; P < 0.01) for linkage. These regions were then fine-mapped in the total sample of 96 families. A single region of chromosome 8q12-q13 was significantly linked to tuberculosis (LOD score = 3.49; P = 3 × 10−5), indicating the presence of a major tuberculosis susceptibility gene. Linkage was stronger (LOD score = 3.94; P = 10−5) in the subsample of 39 families in which one parent was also affected by tuberculosis, whereas it was much lower (LOD score = 0.79) in the 57 remaining families without affected parents, supporting a dominant mode of inheritance of the major susceptibility locus. These results provide direct molecular evidence that human pulmonary tuberculosis has a strong genetic basis, and indicate that the genetic component involves at least one major locus with a dominant susceptibility allele.

Aerosol Exposure System for Rabbits: Application toM. TuberculosisInfection

The development and testing of new antitubercular vaccines and drugs require the use of experimental animal models that resemble pulmonary tuberculosis in humans. We evaluated the effectiveness of an aerosol exposure system for studying experimental pulmonary tuberculosis in rabbits. The device is a snout-only exposure system with 6-animal capacity that uses an individual facemask for each animal. The system is operated from a single jet Bio Aerosol Nebulizing Generator (BANG). The device is placed inside a laminar flow biosafety enclosure, specifically constructed to contain the exposure system. The entire aerosol unit is located within the Animal BSL-3 facility at the Public Health Research Institute (PHRI). After establishing and validating the technical parameters of operation, rabbits were infected via the respiratory route with the avirulent M. bovis strain Bacille Calmette-Guerin (BCG). A suspension of 5–10×106 CFU/ml resulted in 3.6 log10 organisms deposited in the lungs; these were almost fully cleared by 14 days. Next, rabbits were infected with the same infectious dose of the virulent clinical isolate of M. tuberculosis HN878. The bacillary load in the lung at 14 days reached 5.3 log10 CFU and increased progressively. Large granulomatous lesions, distributed evenly in the lung parenchyma developed. We conclude that the aerosol exposure unit is easy to operate, yields a consistent implantation of mycobacteria in the lungs, is safe for the investigators, and induces disease similar to that observed in humans infected with M. tuberculosis.

Mycobacterium africanum: a new opportunistic pathogen in HIV infection?

Mycobacterium africanum, a member of the Mycobacterium tuberculosis complex, is endemic to West Africa, where it causes almost half of pulmonary tuberculosis [1]. Mycobacterium africanum is similar in sequence to M. tuberculosis[2], except that it lacks certain genomic regions, which may account for the lower virulence reported in early animal studies. However, although M. tuberculosis strains with fewer deletions have been associated with reduced rates of pulmonary cavitation [3], there are no reports of differences in clinical presentation or disease course between M. tuberculosis and M. africanum. Although cases of M. africanum have sporadically been identified outside West Africa [4], no chains of transmission have been reported. In Cameroon, M. africanum was identified as causing 56% of pulmonary tuberculosis three decades ago, dropping to 9% in 2001; a new strain of M. tuberculosis accounted for 40% of tuberculosis cases [1]. We hypothesized that M. africanum is a more opportunistic pathogen than M. tuberculosis in HIV-infected subjects. As part of a tuberculosis case contact study in The Gambia, a country with an HIV prevalence of approximately 2%, the mycobacterial isolates from sputum smear-positive tuberculosis index cases were classified by spoligotyping. Isolates were further tested by polymerase chain reaction for RD9 and RD702, two regions of difference that characterize M. africanum subtype I [2]. Patients were tested for HIV-1 and HIV-2 and those who tested positive were referred for HIV clinical care. Of 317 cases, 300 (95%) had an isolate available for analysis, and 286 (90%) had an interpretable spoligotype pattern; 108 (38%) of the isolates were M. africanum and 178 M. tuberculosis. Of the respective index cases 247 consented for HIV testing and 19 (7.7%) tested positive. Cases infected with M. africanum were more likely to be HIV co-infected than those with M. tuberculosis (14 versus 4%, respectively; P = 0.008); conversely 63% of HIV-infected tuberculosis patients were infected with M. africanum, versus 33% of HIV-negative tuberculosis patients. In a logistic regression model, adjusting for age, the odds ratio of HIV infection was 3.2 (95% confidence interval, 1.2–8.6; P = 0.021) when infected with M. africanum compared with M. tuberculosis. A minority of the co-infected patients turned up at the HIV clinic, which precluded analysis by CD4 cell count. Similarly, the numbers of HIV-1, HIV-2 or dually infected patients were too few to seek a specific association by HIV type. We report that M. africanum-infected patients are more likely to be HIV positive than M. tuberculosis-infected patients. The data suggest that M. africanum is more of an opportunist than M. tuberculosis. Within the phylogenetic tree of the M. tuberculosis complex, M. africanum is positioned between M. tuberculosis sensu stricto and Mycobacterium bovis, which was also found to be associated with HIV infection [5]. Mycobacterium bovis has a wider host range and is mainly transmitted from cows through contaminated dairy. It causes up to 7% of human pulmonary tuberculosis in areas where bovine tuberculosis control is poor [6]. Outbreaks of tuberculosis with multi-drug-resistant M. bovis have occurred among HIV-infected patients in nosocomial settings [7], but human-to-human transmission of this organism is an exceptional event in the absence of immune compromise [8]. In contrast, we have found that skin test positivity rates in household contacts of M. africanum cases are similar to those in contacts of M. tuberculosis cases (B. de Jong, unpublished data). Where rates of HIV are low, as was likely to be the case in Cameroon in the 1970s and 1980s, one might expect M. africanum to be out-competed by M. tuberculosis, while increasing HIV prevalence would be associated with an increase in M. tuberculosis strain diversity, including lower virulence strains such as M. africanum. These results highlight new complexities that should be considered when interpreting the changing pattern of important infectious diseases in the presence of an expanding HIV epidemic [9]. If M. africanum is taking advantage of HIV to increase its prevalence then it may well start to appear in other parts of Africa where HIV prevalence is greatest. Further studies typing M. tuberculosis complex strains in HIV cohorts, including studies of M. africanum incidence by CD4 cell count, may delineate its role as an opportunistic infection with respect to HIV in the region and elsewhere in sub-Saharan Africa. Acknowledgement Sponsorship: This work was supported by grant TW06083-01 and by MRC funding.

Validation of housekeeping genes for normalizing RNA expression in real-time PCR.

Analysis of RNA expression using techniques like real-time PCR has traditionally used reference or housekeeping genes to control for error between samples. This practice is being questioned as it becomes increasingly clear that some housekeeping genes may vary considerably in certain biological samples. We used real-time reverse transcription PCR (RT-PCR) to assess the levels of 13 housekeeping genes expressed in peripheral blood mononuclear cell culture and whole blood from healthy individuals and those with tuberculosis. Housekeeping genes were selected from conventionally used ones and from genes reported to be invariant in human T cell culture. None of the commonly used housekeeping genes [e.g., glyceraldehyde-phosphate-dehydrogenase (GAPDH)] were found to be suitable as internal references, as they were highly variable (>30-fold maximal variability). Furthermore, genes previously found to be invariant in human T cell culture also showed large variation in RNA expression (>34-fold maximal variability). Genes that were invariant in blood were highly variable in peripheral blood mononuclear cell culture. Our data show that RNA specifying human acidic ribosomal protein was the most suitable housekeeping gene for normalizing mRNA levels in human pulmonary tuberculosis. Validations of housekeeping genes are highly specific for a particular experimental model and are a crucial component in assessing any new model.

The toll-like receptor 4 Asp299Gly variant: no influence on LPS responsiveness or susceptibility to pulmonary tuberculosis in The Gambia

Setting: Tuberculosis (TB) remains a major cause of morbidity and mortality worldwide. Studies in a murine model of pulmonary TB have identified a role for Toll-like receptor 4 (TLR4) in the development of chronic lung infection with Mycobacterium tuberculosis. The Asp299Gly polymorphism in the human TLR4 gene is associated with in vivo hyporesponsiveness to lipopolysaccharide (LPS) in Caucasians. Objective: To determine whether TLR4 Asp299Gly influences LPS responses or susceptibility to pulmonary TB in humans in a Gambian population sample. Design: We compared whole blood monokine responses to LPS in 245 healthy blood donors stratified by TLR4 Asp299Gly genotype to assess whether this polymorphism was functional in this population. A case-control study of 640 subjects was conducted to investigate whether TLR4 Asp299Gly was associated with TB. Results: LPS-induced tumour necrosis factor, interleukin-1 β and interleukin-10 production was not influenced by TLR4 Asp299Gly genotype. There was no association between TLR4 Asp299Gly and TB. Conclusion: Our data suggest that TLR4 Asp299Gly has no influence on monocyte LPS responses or susceptibility to TB in Gambians and could be an ancient neutral polymorphism.

Morphometric analysis of Th 1 and Th 2 cytokine expression in human pulmonary tuberculosis

Following infection with Mycobacterium tuberculosis, host cytokine responses influence disease manifestation. Differences in cytokine expression likely determine whether tuberculosis (TB) progresses, resolves, or becomes latent. In particular, the balance between Th(1) and Th(2) cytokine responses influences the expression of disease in individuals with pulmonary TB. Since the cytokine microenvironment in pulmonary TB remains suboptimally defined, we utilized quantitative immunohistochemistry to compare the expression of Th(1) cytokines [interferon-gamma (IFNgamma) and interleukin-12 (IL-12)] and Th(2) cytokines [IL-4, IL-10, transforming growth factor-beta (TGFbeta)] in surgically resected lungs of seven TB patients and four control subjects. We also quantified IFNgamma-inducible protein 10 (IP-10) expression, a CXC chemokine for macrophages and T cells. Morphometric analyses revealed increased IFNgamma, IL-12, IP-10, and TGFbeta in granulomas and in pneumonitis areas of TB lungs. In contrast, IL-10 and IL-4 expressions were globally reduced in TB lung tissues compared to controls. Th(1) cytokines and TGFbeta are increased while Th(2) cytokines are decreased in well-formed pulmonary granulomas of TB patients compared to controls.

Immunophenotyping of macrophages in human pulmonary tuberculosis and sarcoidosis.

Classic studies of tuberculosis (TB) revealed morphologic evidence of considerable heterogeneity of macrophages (MØs), but the functional significance of this heterogeneity remains unknown. We have used newly available specific antibodies for selected membrane and secretory molecules to examine the phenotype of MØs in situ in a range of South African patients with TB, compared with sarcoidosis. Patients were human immunodeficiency virus-negative adults and children, and the examined biopsy specimens included lung and lymph nodes. Mature pulmonary MØs (alveolar, interstitial, epithelioid and multinucleated giant cells) selectively expressed scavenger receptor type A and a novel carboxypeptidase-like antigen called carboxypeptidase-related vitellogenin-like MØ molecule (CPVL). CPVL did not display enhanced expression in sarcoidosis, vs. TB patients, as observed with angiotensin-converting enzyme (ACE), a related molecule. Immunocytochemical studies with surfactant proteins (SP)-A and -D showed that type II alveolar cells expressed these collectins, as did MØs, possibly after binding of secreted proteins. Studies with an antibody specific for the C-terminus of fractalkine, a tethered CX3C chemokine, confirmed synthesis of this molecule by bronchiolar epithelial cells and occasional endothelial cells. These studies provide new marker antigens and extend previous studies on MØ differentiation, activation and local interactions in chronic human granulomatous inflammation in the lung.

Monocyte chemotactic protein-1 production in patients with active pulmonary tuberculosis and tuberculous pleurisy.

The role of monocyte chemotactic protein (MCP)-1 in human pulmonary and pleural tuberculosis (TB) was assessed by examining its production in clinical samples from patients with active pulmonary TB and tuberculous pleurisy (TBP). Serum was obtained from 26 active pulmonary TB patients [14 early TB (E-TB), and 12 chronic refractory TB (CR-TB)] and 15 healthy tuberculin reactors (HTRs). The monocytes and peripheral blood mononuclear cells (PBMCs) were separated and stimulated with purified protein derivatives (PPD) or the 30-kDa antigen of Mycobacterium tuberculosis. Pleural exudates were isolated from 25 patients with TBP and 24 non-TBP patients [malignancy and congestive heart failure (CHF)]. The MCP-1 levels were measured by enzyme-linked immunosorbent assay (ELISA). In sera, the MCP-1 levels of TB patients were similar to those of HTRs. For monocytes, CR-TB patients spontaneously expressed more MCP-1, compared with HTRs and E-TB patients. In addition, MCP-1 production of PPD- or 30-kDa antigen-stimulated monocytes was significantly elevated in CR-TB patients than that from E-TB. Interestingly, the E-TB patients had significantly depressed MCP-1 production by PBMCs in response to PPD or 30-kDa, compared with HTRs and CR-TB patients. In pleural effusions, MCP-1 levels were significantly higher in patients with TBP than in patients with CHF, but lower than in malignant effusions. The data suggest that MCP-1 production is not uniquely elevated systemically in TB patients, although MCP-1 production might be elevated by monocytes in the chronic phase of TB or with a local pleural infection.

A short history of Robert Koch's fight against tuberculosis: Those who do not remember the past are condemned to repeat it

The Fourth World Congress on Tuberculosis was not the first international congress on this topic to be held in Washington. Already in 1908, the International Congress on Tuberculosis convened in Washington. At the opening of this congress on September 28th, Koch was elected to the post of honorary president. He delivered his lecture on September 30th, in a symposium chaired by Prof. Welch, a pathologist from the Johns Hopkins University, Baltimore. The lecture dealt with the relationship between human and bovine tuberculosis. In Koch’s opinion, human pulmonary tuberculosis could not be transmitted by the bovine pathogen:

Leptin and energy metabolism in pulmonary tuberculosis

Pulmonary tuberculosis is the classic cause of "consumption," but the pathogenesis of such wasting is largely unknown. Animal studies in other conditions suggest that leptin may be a mediator between proinflammatory cytokine activity and wasting. We tested whether the leptin concentration, after control for body fat mass, is higher during active pulmonary tuberculosis than after recovery and whether it correlates with energy metabolism and proinflammatory cytokine activity. Nondiabetic adults with pulmonary tuberculosis (n = 32) were recruited into a prospective observational study. Patients found to be antibody positive for human immunodeficiency virus were excluded from the study. Dual-energy X-ray absorptiometry, indirect calorimetry, and food intake protocols were performed at baseline and after 1 and 6 mo of tuberculosis treatment. Fasting plasma leptin, tumor necrosis factor alpha and its soluble receptor, and interleukin 6 were measured by enzyme-linked immunosorbent assay. Resting energy expenditure was close to Harris-Benedict predictions and did not change significantly during treatment, but energy intake increased. Leptin concentration was correlated in a log-linear fashion with percentage body fat but was independent of cytokines and energy intake. There was no significant difference in leptin, corrected for energy balance and fat mass, at baseline and after 1 and 6 mo of treatment. These data are compatible with recovery from anorexia or starvation without discernible hyper- or hypometabolism. The close correlation of leptin with body fat mass is similar to observations in healthy subjects. No additional influence of disease state or proinflammatory cytokine activity was found. Leptin does not appear to be a component of the immune response to human pulmonary tuberculosis, and thus it cannot account for the weight loss and anorexia associated with tuberculosis.

Analysis of nitric oxide synthase and nitrotyrosine expression in human pulmonary tuberculosis.

The role of nitric oxide (NO) in the host-defense against human tuberculosis (TB) is controversial. Although experimental evidence indicates that NO may play an important role in controlling TB, its expression in human tuberculous lungs has not been systematically characterized. We therefore investigated the expression of NO synthases (NOS) and of nitrotyrosine, the latter a marker of NO expression, in surgically resected lungs of eight patients with TB. Immunohistochemical and morphometric analyses revealed that, compared with control subjects, inducible NOS, endothelial NOS, and nitrotyrosine, but not neuronal NOS, were significantly elevated in the inflammatory zone of the tuberculous granulomas, and in the nongranulomatous pneumonitis zone. Tumor necrosis factor-alpha (TNF-alpha) was also significantly increased in tuberculous lungs and was principally localized to the necrotic, and to a lesser extent, the inflammatory and fibrotic areas of the granulomas. The NOS isoforms, nitrotyrosine, and TNF-alpha were expressed by the epithelioid macrophages and giant cells within the granulomas and in alveolar macrophages and epithelial cells in pneumonitis areas. This descriptive study provides evidence that in human TB, NOS isoenzymes and NO are present in specialized areas of the tuberculous granulomas; their precise role in human TB remains to be determined.

Preferential recruitment of phagocytes into the lung of patients with advanced acquired immunodeficiency syndrome and tuberculosis

Limited data are available on the cellular and immunocytological characteristics of bronchoalveolar lavage (BAL) fluid in individuals infected with the human immunodeficiency virus (HIV) and pulmonary tuberculosis (TB). The immune host response against tuberculosis in early HIV-infection may differ from that in later stages of HIV disease, as is strongly suggested by different clinical and radiographic patterns. We studied the cellular elements in the lungs of 15 HIV-infected patients with advanced immunosuppression and pulmonary tuberculosis (TB/AIDS). The findings were compared with data from four other groups: 1) 15 HIV-seronegative patients with pulmonary TB; 2) 12 HIV-seropositive TB patients without previous AIDS-defining illnesses and with CD4+>200 cells mm−3; 3) five AIDS patients without pulmonary lesions; and 4) five healthy controls. BAL fluid and differential cell counts, as well as lymphocyte subsets, were determined. Despite a low CD4/CD8 ratio, the TB/AIDS group had a higher absolute number of CD8+ lymphocytes in the BAL fluid than the other groups. Alveolar macrophages and neutrophils were significantly increased in TB/AIDS patients compared to control groups. The number of eosinophils was increased in TB/HIV−patients but not in TB/AIDS patients. We conclude that tuberculosis in late stage HIV-infected patients has a distinct inflammatory cell profile, suggesting an enhanced compensatory mechanism that amplifies the unspecific inflammatory reaction.

Whole body protein metabolism in human pulmonary tuberculosis and undernutrition: evidence for anabolic block in tuberculosis.

1. Differing patterns of protein metabolism are seen in wasting due to undernutrition and wasting due to chronic infection. 2. We investigated whole body energy and protein metabolism in nine subjects with pulmonary tuberculosis, six undernourished subjects (body mass index < 18.5 kg/m2) and seven control subjects from an Indian population. Fasting subjects were infused with L-[1-13C]leucine (2.3 mumol.h-1.kg-1) for 8 h, 4 h fasted then 4 h fed. Leucine kinetics were derived from 13C-enrichment of leucine and alpha-ketoisocaproic acid in plasma and CO2 in breath. 3. Undernourished subjects, but not tuberculosis subjects, had higher rates of whole body protein turnover per unit lean body mass than controls [163.1 +/- 9.4 and 148.6 +/- 14.6 mumol compared with 142.8 +/- 14.7 mumol leucine/h per kg, based on alpha-ketoisocaproic acid enrichment (P = 0.039)]. 4. In response to feeding, protein oxidation increased in all groups. Tuberculosis subjects had the highest fed rates of oxidation (47.0 +/- 10.5 compared with 37.1 +/- 5.4 mumol.h-1.kg-1 in controls), resulting in a less positive net protein balance in the fed phase (controls, 39.7 +/- 6.2; undernourished subjects, 29.2 +/- 10.6; tuberculosis subjects, 24.5 +/- 9.3; P = 0.010). Thus fed-phase tuberculosis subjects oxidized a greater proportion of leucine flux (33.2%) than either of the other groups (controls, 24.0%; undernourished subjects, 24.0%; P = 0.017). 5. Tuberculosis did not increase fasting whole body protein turnover but impaired the anabolic response to feeding compared with control and undernourished subjects. Such 'anabolic block' may contribute to wasting in tuberculosis and may represent the mechanism by which some inflammatory states remain refractory to nutrition support.

Letter: Flow cytometric study of T-cell subsets in lymphocytic pleural effusions

CytometryVolume 30, Issue 4 p. 204-205 Forum: Letters & CommentaryFree Access Letter: Flow cytometric study of T-cell subsets in lymphocytic pleural effusions Rasha Y. Khalil, Corresponding Author Rasha Y. Khalil Departments of Immunology and Microbiology, Faculty of Medicine, Ain Shams University, Cairo, EgyptDepartments of Immunology and Microbiology, Faculty of Medicine, Ain Shams University, Cairo, EgyptSearch for more papers by this authorMadgy M. Khalil, Madgy M. Khalil Department of Chest Diseases, Faculty of Medicine, Ain Shams University, Cairo, EgyptSearch for more papers by this author Rasha Y. Khalil, Corresponding Author Rasha Y. Khalil Departments of Immunology and Microbiology, Faculty of Medicine, Ain Shams University, Cairo, EgyptDepartments of Immunology and Microbiology, Faculty of Medicine, Ain Shams University, Cairo, EgyptSearch for more papers by this authorMadgy M. Khalil, Madgy M. Khalil Department of Chest Diseases, Faculty of Medicine, Ain Shams University, Cairo, EgyptSearch for more papers by this author First published: 26 December 2002 https://doi.org/10.1002/(SICI)1097-0320(19970815)30:4<204::AID-CYTO8>3.0.CO;2-JCitations: 4AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. Literature Cited 1 Ainsle GS, Solomon JA, Bateman ED: Lymphocyte and lymphocyte subset numbers in blood and in bronchoalveolar lavage and pleural fluid in various forms of human pulmonary tuberculosis at presentation and during recovery. Thorax 47: 513– 518, 1992. 2 Barnes PF, Mistry SD, Cooper CL, Pirmez C, Rea TH, Modlin RL: Compartimentalization of a CD4+ T-lymphocyte subpopulation in tuberculous pleuritis. J Immunol 142: 1114– 1119, 1989. 3 Hamaoka T, Fujiwara H: Phenotypically and functionally distinct T-cell subsets in antitumor responses. Immunol Today 8: 267– 269, 1987. Citing Literature Volume30, Issue415 August 1997Pages 204-205 ReferencesRelatedInformation

Characterization of the Multinucleated Giant Cell Glycoconjugates in the Tubercle of Human Pulmonary Tuberculosis

Characterization of the Multinucleated Giant Cell Glycoconjugates in the Tubercle of Human Pulmonary Tuberculosis

Mycobacterium fortuitum glycolipids for the serodiagnosis of pulmonary tuberculosis.

Glycolipids belonging to the family of acylated trehaloses were isolated from Mycobacterium fortuitum, a rapidly growing mycobacterial species, and tested in the serologic diagnosis of human pulmonary tuberculosis by enzyme-linked immunosorbent assay. Di- and tri-O-acylated trehaloses from M. fortuitum reacted with serum antibodies of patients with pulmonary tuberculosis at higher titers than did with sera from healthy donors. With both glycolipids, the sensitivity of the test was above 0.80 at a chosen specificity of 0.98. Individuals with treated tuberculosis showed lower antibody titers compared with their initial reactivities. These data show that M. fortuitum could be used as a surrogate source of antigens for tuberculosis serodiagnosis.

Cavitary tuberculosis produced in rabbits by aerosolized virulent tubercle bacilli.

Liquefaction of solid caseous tuberculous lesions and the subsequent cavity formation are probably the most dangerous processes in the pathogenesis of human pulmonary tuberculosis. In liquefied caseum, the tubercle bacilli grow extracellularly for the first time since the onset of the disease and can reach such large numbers that mutants with antimicrobial resistance may develop. From a cavity, the bacilli enter the bronchial tree and spread to other parts of the lung and also to other people. Of the commonly used laboratory animals, the rabbit is the only one in which cavitary tuberculosis can be readily produced. This report is the first to describe and analyze the complete course of cavitary tuberculosis, produced by aerosolized virulent bovine-type tubercle bacilli in commercially available New Zealand white rabbits. After the inhalation of 220 to 880 bacillary units, all of the rabbits were overtly well until they were sacrificed at 33 weeks. After the inhalation of 3,900 to 5,800 bacillary units, half of the rabbits died of progressive tuberculosis between 5 and 9 weeks and the other half lived until they were sacrificed at 18 weeks. Pulmonary cavities developed in both low- and high-dose groups, some beginning as early as 6 weeks. Bacilli from primary cavities sometimes caused nearby secondary cavities, but more frequently, they ascended the bronchial escalator, were swallowed, and caused secondary tubercles in the lymphoid tissue of the appendix and ileocecal junction. Histologically, and by culture, the number of bacilli found in the liquefied caseum varied from many to comparatively few. Strong tuberculin reactions at 4 weeks after infection were associated with fewer primary lesions, while strong tuberculin reactions at 33 weeks were associated with more cavitary lesions. In the tuberculous granulation tissue surrounding caseous and liquefied pulmonary foci and cavities, we found many mature epithelioid macrophages that contained high levels of the proteinase cathepsin D. Therefore, cathepsin D probably plays a major role in the liquefaction of solid caseous material and in the subsequent cavity formation.