Increased specific T cell cytokine responses in patients with active pulmonary tuberculosis from Central Africa

An understanding of T cell responses that are crucial for control of Mycobacterium tuberculosis (MTB) has major implications for the development of immune-based interventions. We studied the frequency of purified protein derivative (PPD)-specific CD3) cells expressing interleukin-2 (IL)-2, gamma interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha and IL-10 in HIV-negative pulmonary tuberculosis patients (TB, n=30) as well as in healthy individuals (controls, n=21) from Central Africa. Increased frequencies of PPD-stimulated CD3+ cells expressing IL-2, IFN-gamma, and TNF-alpha in TB were seen when compared with frequencies of controls. The presence of type 1 cytokine biased responses in TB patients was supported by a shift in the distribution pattern of cytokine expression from exclusively IL-2 or TNF-alpha expression seen in controls towards an increased frequency of IFN-gamma/IL-2 or IFN-gamma/TNF-alpha co-expression in TB. Higher levels of PPD-induced IFN-gamma in the supernatants from TB patients than from controls were found, which correlated with its intracellular expression. PPD was a weak inducer of IL-10 in T cells and insufficient in promoting cytokine production in TCRgammadelta+CD3+ cells. Non-specific stimulation with PMA and ionomycin revealed increased frequencies of CD4+ cells expressing IFN-gamma in controls, while expression of IL-2, IL-4, IL-10, IL-13, and TNF-alpha was not different. Non-specific cytokine responses of TCRgammadelta+CD3+ cells were similar in all groups. Pulmonary TB in Central Africa is associated with enhanced expression and secretion of specifically induced cytokines that are frequently implicated in host defense against MTB.     

CXCL10/IP-10 release is induced by incubation of whole blood from tuberculosis patients with ESAT-6, CFP10 and TB7.7

IFN-gamma responses to Mycobacterium tuberculosis specific antigens are used as in vitro diagnostic tests for tuberculosis infection. The tests are sensitive and specific for latent and active tuberculosis disease, but sensitivity may be reduced during immunosuppression. The objective of the study was to explore new ways to improve the diagnosis of tuberculosis infection using CXCL10 and IL-2 as alternative markers to IFN-gamma. CXCL10, IL-2, and IFN-gamma responses to stimulation with ESAT-6/CFP10/TB7.7 were assessed in 12 Quantiferon positive, 8 Quantiferon negative tuberculosis patients and 11 Quantiferon negative controls. CXCL10 and IL-2 were determined by multiplex and IFN-gamma by the Quantiferon ELISA. The median antigen specific CXCL10, IFN-gamma, and IL-2 responses in patients with tuberculosis were 870 pg/ml (range 261-1576 pg/ml), 217 pg/ml (81-1273 pg/ml), 59 pg/ml (14-276 pg/ml) respectively, and the CXCL10 responses were significantly higher than any of the other cytokines measured (p=0.001). In 4/7 individuals with a negative (n=6) or indeterminate (n=1) Quantiferon test, antigen specific CXCL10 responses were detectable at high levels ranging from 196-532 pg/ml. In conclusion CXCL10 was strongly induced after M. tuberculosis specific stimulation and sensitivity appeared superior to the Quantiferon test. Our findings suggest that CXCL10 may serve as an alternative or additional marker for the immunodiagnosis of tuberculosis.     

Interferon gamma response to combinations 38 kDa/CFP-10, 38 kDa/MPT-64, ESAT-6/MPT-64 and ESAT-6/CFP-10, each related to a single recombinant protein of Mycobacterium tuberculosis in individuals from tuberculosis endemic areas

Several antigens of Mycobacterium tuberculosis have been identified and specificity to one or multiple antigens could determine the distinction between protective and pathogenic host reaction. Therefore T cell immune response to combinations 38 kDa/CFP-10, 38 kDa/MPT-64, ESAT-6/MPT-64 and ESAT-6/CFP-10 (each related to a single protein of Mycobacterium tuberculosis) in individuals from tuberculosis endemic areas have been examined. ELISA was used to detect IFN-gamma production in PBMC priming with single proteins and combinations in a panel of 105 individuals: 38 tuberculosis patients (6 untreated and 32 treated) and 67 healthy controls with tuberculin skin test positive or negative (TST). Brazilian TB patients highly recognized ESAT-6 (66%), but combinations improved response in the following order: ESAT-6/MPT-64 (89%) > ESAT-6/CFP-10 (73%) > 38 kDa/CFP-10 (70%), the last combination showing the highest specificity (TST(/) = 42% and TST(-) = 83%). Average IFN-gamma production in TB patients was signifi-cantly higher for 38 kDa/CFP-10 (P = 0.012) and 38 kDa/MPT-64 (P <0.035), when compared to single antigens. None of the combinations was able to discriminate TB patients from TST(+) controls; however, 38 kDa/CFP-10 displayed a borderline significance (P = 0.053). Similar to the ESAT-6/CFP-10 combination, IFN-gamma response to 38 kDa/CFP-10 showed an increased tendency in treated patients, although not signifi-cant (P = 0.16). We demonstrated for the first time that 38 kDa/CFP-10 had prediction sensitivity for TB patients similar to the ESAT-6/CFP-10 combination and also significant response improvement related to the single proteins with more selective reactivity among TST-positive individuals, which could be of potential interest for diagnostic evaluation for tuberculosis infection.     

Association of tuberculosis and polymorphisms in the promoter region of macrophage migration inhibitory factor (MIF) in a Southwestern China Han population

The macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine that plays an important role in the pathogenesis of immune diseases. High levels of MIF have been detected in the sera of patients with tuberculosis (TB), and it has been proposed that MIF gene polymorphisms may influence the risk of developing TB. The aim of this study was to evaluate the potential relationship between functional polymorphisms of MIF and TB in a Han population from Southwestern China. TB patients (n=215) and healthy unrelated controls (n=245) were recruited for this study. Genomic DNA was isolated from all the participants. The MIF-173 G/C SNP was genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The MIF-794 CATT(5-8) microsatellite was evaluated by direct sequencing of the subsequent PCR products. Association analysis of the two polymorphisms showed that the frequency of -173 (GC+CC) in TB patients and controls was 49.3% and 31.4%, respectively, which was statistically significant (OR=2.12, 95% CI=1.45-3.10, P<0.001); the frequencies of -794 (7/X+8/X) were 56.7% and 45.3%, respectively, also statistically significant between the TB and healthy controls (OR=1.58, 95% CI=1.10-2.29, P=0.015). In summary, Genetic variation in the MIF gene is closely associated with tuberculosis. Both the 173 (GC+CC) SNP and -794 (7/X+8/X) microsatellite increased the risk of Chinese Han developing TB.     

Cell proliferation and interferon-gamma response to recombinant MBP-3, NarL, MT-10.3, and 16 kDa 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.     

Analysis of Plasma Cytokine and Chemokine Profiles in Patients with and without Tuberculosis by Liquid Array-Based Multiplexed Immunoassays

The aim of this study was to establish plasma cytokine/chemokine profiles in patients with 3 different presentations of active tuberculosis (TB), compared to the profiles observed in bacillus Calmette-Guérin (BCG)-vaccinated healthy individuals and patients with other pulmonary diseases (non-TB patients). To this end, plasma samples were collected from 151 TB patients including 68 pulmonary TB (PTB), 43 endobronchial TB, and 40 tuberculosis pleurisy (TP) patients, as well as 107 no-TB cases including 26 non-TB patients and 81 BCG-vaccinated healthy controls. A liquid array-based multiplexed immunoassay was used to screen plasma samples for 20 distinct cytokines and chemokines. Multinomial logistic regression was used to analyze associations between cytokines/chemokines and TB/non-TB patients. Compared to our findings with the no-TB donors, the median plasma levels of the proinflammatory cytokines/chemokines TNF-α, IL-6, IP-10, IFN-γ, and MIP-1β were significantly elevated in TB patients, suggesting their potential use as biomarkers for diagnosing TB patients. Further comparisons with healthy donors showed that only the median TNF-α plasma level was highly produced in the plasma of all 3 types of TB patients. Plasma IL-6 production was higher only in TP patients, while the plasma levels of IP-10, IFN-γ, and MIP-1β were markedly enhanced in both PTB and TP patients. Unexpectedly, among the above cytokines/chemokines, MIP-1β was also highly expressed in non-TB patients, compared with healthy donors. Our results suggested that TNF-α may be an ideal biomarker for diagnosing the 3 forms of TB presentation, while the other factors (IL-6, IP-10, MCP-1, and IFN-γ) can potentially facilitate differential diagnosis for the 3 TB presentation types. Further characterization of immune responses associated with different types of TB diseases will provide a basis for developing novel TB diagnostics.     

利用rCFP-10/ESAT-6融合蛋白刺激γ-IFN体外释放测定替代结素皮试检出结核感染的可行性

评估rCFP-10/ESAT-6融合蛋白刺激γ-IFN体外释放测定与结素皮试检出结核感染的敏感性及特异性。对疑似结核病患者共229例进行随机、双盲、平行、对照、前瞻性试验,后经细菌培养证实患结核病的病人共129人,没有结核病史的非结核病患者共100人。以某一特定的γ-IFN体外释放水平及结素皮试反应硬结直径?10 mm为阳性切割值,rCFP-10/ESAT-6融合蛋白刺激γ-IFN体外释放测定的敏感性为96%,显著高于结素皮试(89%)(χ2=4.92;0.025相似文献   

Plasma Metabolomics in Human Pulmonary Tuberculosis Disease: A Pilot Study

We aimed to characterize metabolites during tuberculosis (TB) disease and identify new pathophysiologic pathways involved in infection as well as biomarkers of TB onset, progression and resolution. Such data may inform development of new anti-tuberculosis drugs. Plasma samples from adults with newly diagnosed pulmonary TB disease and their matched, asymptomatic, sputum culture-negative household contacts were analyzed using liquid chromatography high-resolution mass spectrometry (LC-MS) to identify metabolites. Statistical and bioinformatics methods were used to select accurate mass/charge (m/z) ions that were significantly different between the two groups at a false discovery rate (FDR) of q<0.05. Two-way hierarchical cluster analysis (HCA) was used to identify clusters of ions contributing to separation of cases and controls, and metabolomics databases were used to match these ions to known metabolites. Identity of specific D-series resolvins, glutamate and Mycobacterium tuberculosis (Mtb)-derived trehalose-6-mycolate was confirmed using LC-MS/MS analysis. Over 23,000 metabolites were detected in untargeted metabolomic analysis and 61 metabolites were significantly different between the two groups. HCA revealed 8 metabolite clusters containing metabolites largely upregulated in patients with TB disease, including anti-TB drugs, glutamate, choline derivatives, Mycobacterium tuberculosis-derived cell wall glycolipids (trehalose-6-mycolate and phosphatidylinositol) and pro-resolving lipid mediators of inflammation, known to stimulate resolution, efferocytosis and microbial killing. The resolvins were confirmed to be RvD1, aspirin-triggered RvD1, and RvD2. This study shows that high-resolution metabolomic analysis can differentiate patients with active TB disease from their asymptomatic household contacts. Specific metabolites upregulated in the plasma of patients with active TB disease, including Mtb-derived glycolipids and resolvins, have potential as biomarkers and may reveal pathways involved in TB disease pathogenesis and resolution.     

PD-1, PD-L1 and PD-L2 Gene Expression on T-Cells and Natural Killer Cells Declines in Conjunction with a Reduction in PD-1 Protein during the Intensive Phase of Tuberculosis Treatment

Background

The PD-1 axis is a cell intrinsic immunoregulatory pathway that mediates T cell exhaustion in chronic infection particularly in some viral infections. We hypothesized that PD-1, PD-L1 and PD-L2 would be highly expressed in untreated tuberculosis patients compared to controls due to their chronic infection and would decrease with successful TB treatment.

Materials and Methods

Untreated tuberculosis patients (n = 26) were recruited at diagnosis and followed up during treatment. Household contacts (n = 24) were recruited to establish baseline differences. Blood gene expression ex vivo was investigated using qRT-PCR. Flow cytometry was performed to establish protein expression patterns.

Results

PD-L1 gene expression was found to be elevated in active TB disease; however, this was not observed for PD-1 or PD-L2. The intensive phase of TB treatment was associated with a significant decline in PD-1, PD-L1 and PD-L2 gene expression. PD-1 protein expression on the surface of NK cells, CD8⁺ and CD4⁺ T cells was similar in patients with active TB disease compared to controls but declined with successful TB treatment, with the greatest decline occurring on the NK cells followed by CD8⁺ T cells and then CD4⁺ T cells. Granzyme B/PD-1 co-expression declined with successful intensive phase treatment.

Conclusion

Modulation of PD-1/PD-L1 pathway through TB treatment indicates changes in the peripheral T cell response caused by live Mycobacterium tuberculosis (Mtb) followed by the response to dead bacilli, antigen-release and immuno-pathology resolution. The PD-1 axis could be a host drug target for immunomodulatory treatments in the future.     

Decreased plasma granulysin and increased interferon-gamma concentrations in patients with newly diagnosed and relapsed tuberculosis

Granulysin and interferon-gamma (IFN-γ) have broad antimicrobial activity which controls Mycobacterium tuberculosis (M. tuberculosis) infection. Circulating granulysin and IFN-γ concentrations were measured and correlated with clinical disease in Thai patients with newly diagnosed, relapsed and chronic tuberculosis (TB). Compared to controls, patients with newly diagnosed, relapsed and chronic TB had lower circulating granulysin concentrations, these differences being significant only in newly diagnosed and relapsed TB (P < 0.001 and 0.004, respectively). Granulysin concentrations in patients with newly diagnosed and relapsed TB were significantly lower than in those with chronic TB (P= 0.003 and P= 0.022, respectively). In contrast, significantly higher circulating IFN-γ concentrations were found in patients with newly diagnosed and relapsed TB compared to controls (P < 0.001). The IFN-γ concentrations in newly diagnosed and relapsed patients were not significantly different from those of patients with chronic TB. However, in vitro stimulation of peripheral blood mononuclear cells (PBMCs) from patients with newly diagnosed, relapsed and chronic TB with purified protein derivative (PPD) or heat killed M. tuberculosis (H37Ra) enhanced production of granulysin by PBMCs. In vitro, stimulation of PBMCs of newly diagnosed TB patients with PPD produced greater amounts of IFN-γ than did controls, while those stimulated with H37Ra did not. The results demonstrate that patients with active pulmonary TB have low circulating granulysin but high IFN-γ concentrations, suggesting possible roles in host defense against M. tuberculosis for these agents.     

Common MCL1 polymorphisms associated with risk of tuberculosis

MCL1 expression has been found to be up-regulated during infection with virulent Mycobacterium tuberculosis. We investigated the genetic polymorphisms in MCL1 as potential candidate gene for a host genetic study of clinical TB infection. We have sequenced exons and their boundaries of MCL1, including the 1.5 kb promoter region, to identify polymorphisms, and eight polymorphisms were identified. The genetic associations of polymorphisms in MCL1 with clinical TB patients (n=486) and normal controls (n=370) were analyzed. Using statistical analyses, one common promoter polymorphism (MCL1- 324C > A) which is absolutely linked with three other SNPs in the promoter and 3'UTR regions, were found to be significantly associated with increased risk of clinical TB disease. The frequency of the A-bearing genotype of -324C > A was higher in clinical TB patients than in normal controls (P=0.0008, OR= 1.68). Our findings suggest that polymorphisms in MCL1 might be one of genetic factors for the risk of clinical tuberculosis development.     

Healthy individuals that control a latent infection with Mycobacterium tuberculosis express high levels of Th1 cytokines and the IL-4 antagonist IL-4delta2

The majority of healthy individuals exposed to Mycobacterium tuberculosis will not develop disease and identifying what constitutes "protective immunity" is one of the holy grails of M. tuberculosis immunology. It is known that IFN-gamma is essential for protection, but it is also apparent that IFN-gamma levels alone do not explain the immunity/susceptibility dichotomy. The controversy regarding correlates of immunity persists because identifying infected but healthy individuals (those who are immune) has been problematic. We have therefore used recognition of the M. tuberculosis virulence factor early secretory antigenic target 6 to identify healthy, but infected individuals from tuberculosis (TB)-endemic and nonendemic regions (Ethiopia and Denmark) and have compared signals for cytokines expressed directly ex vivo with the pattern found in TB patients. We find that TB patients are characterized by decreased levels of Th1 cytokines and increased levels of IL-10 compared with the healthy infected and noninfected community controls. Interestingly, the healthy infected subjects exhibited a selective increase of message for the IL-4 antagonist, IL-4delta2, compared with both TB patients or noninfected individuals. These data suggest that long-term control of M. tuberculosis infection is associated not just with elevated Th1 responses but also with inhibition of the Th2 response.     

CD14 gene promoter polymorphism in different clinical forms of tuberculosis

Mycobacterium tuberculosis interacts with monocyte-macrophages through cell surface molecules including CD14. A soluble form of CD14 (sCD14) exists in human serum, and higher amounts of it are found in tuberculosis. A polymorphism on CD14 gene promoter was associated with increased sCD14 levels in some diseases. To evaluate whether this polymorphism associates with tuberculosis, its clinical forms, and increased sCD14, genotype/allele frequencies in tuberculosis patients were compared with the controls. Results confirmed increased levels of sCD14 in patients with tuberculosis, and those with miliary tuberculosis had the highest levels. sCD14 decreased to normal levels after anti-tuberculosis treatment. No association was found between the CD14 polymorphism and tuberculosis or sCD14 levels. Results suggest that sCD14 may be involved in anti-tuberculosis immune response, but its increase is a consequence of infection rather than a predisposed genetic trait. Measuring sCD14 in tuberculosis may help monitor anti-tuberculosis treatment.     

Gamma delta T cell responses associated with the development of tuberculosis in health care workers

This study evaluated T cell immune responses to purified protein derivative (PPD) and Mycobacterium tuberculosis (Mtb) in health care workers who remained free of active tuberculosis (HCWs w/o TB), health care workers who went on to develop active TB (HCWs w/TB), non-health care workers who were TB free (Non-HCWs) and tuberculosis patients presenting with minimal (Min TB) or advanced (Adv TB) disease. Peripheral blood mononuclear cells (PBMC) were stimulated with Mtb and PPD and the expression of T cell activation markers CD25+ and HLA-DR+, intracellular IL-4 and IFN-gamma production and cytotoxic responses were evaluated. PBMC from HCWs who developed TB showed decreased percentages of cells expressing CD8+CD25+ in comparison to HCWs who remained healthy. HCWs who developed TB showed increased gammadelta TCR+ cell cytotoxicity and decreased CD3+gammadelta TCR- cell cytotoxicity in comparison to HCWs who remained healthy. PBMC from TB patients with advanced disease showed decreased percentages of CD25+CD4+ and CD25+CD8+ T cells that were associated with increased IL-4 production in CD8+ and gammadelta TCR+ phenotypes, in comparison with TB patients presenting minimal disease. TB patients with advanced disease showed increased gammadelta TCR+ cytotoxicity and reduced CD3+gammadelta TCR- cell cytotoxicity. Our results suggest that HCWs who developed TB show an early compensatory mechanism involving an increase in lytic responses of gammadelta TCR+ cells which did not prevent TB.     

Differential Levels of Alpha-2-Macroglobulin,Haptoglobin and Sero-Transferrin as Adjunct Markers for TB Diagnosis and Disease Progression in the Malnourished Tribal Population of Melghat,India

Lack of diagnostic capacity has been a crucial barrier preventing an effective response to the challenges of malnutrition and tuberculosis (TB). Point-of-care diagnostic tests for TB in immuno-incompetent, malnourished population are thus needed to ensure rapid and accurate detection. The aim of the study was to identify potential biomarkers specific for TB infection and progression to overt disease in the malnourished population of Melghat. A prospective cohort study was conducted in the year 2009 through 2011 in six villages of the Melghat region. 275 participants consisting of malnourished cases with a) active TB (n = 32), b) latent TB infection (n = 90), c) with no clinical or bacteriological signs of active or latent TB (n = 130) and healthy control subjects (n = 23) were recruited for the study. The proteome changes of the host serum in response to Mycobacterium tuberculosis (M.tb) infection were investigated using one dimensional electrophoresis in combination with matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Three most differentially expressed proteins; alpha-2-macroglobulin (A-2-M), sero-transferrin and haptoglobin were identified by MALDI-TOF MS analysis, which were up-regulated in the malnourished patients with active TB and down-regulated in the malnourished patients compared with the healthy controls. Additionally, follow-up studies indicated that the expression of these proteins increased to nearly two folds in patients who developed active disease from latent state. Our preliminary results suggest that A-2-M, sero-transferrin and haptoglobin may be clinically relevant host biomarkers for TB diagnosis and disease progression in the malnourished population. This study provides preliminary framework for an in-depth analysis of the biomarkers in larger well-characterized cohorts. Evaluation of these biomarkers in follow-up cases may further aid in improving TB diagnosis.     

Functional and phenotypic changes in monocytes from patients with tuberculosis are reversed with treatment

Alterations of monocyte/macrophages have been reported in patients with tuberculosis (TB), but their significance is poorly understood. Blood mononuclear cells from patients with different clinical forms of TB, at various times of anti-TB treatment, and healthy tuberculin positive individuals, were double-stained for CD14 plus CD206, TLR-2, IFN-gammaR1, CD40, HLA-DR, CD36 and CD163, and analyzed by flow cytometry. Monocytes were infected with Mycobacterium tuberculosis H37Rv and 24h later the phenotype, induction of necrosis and apoptosis and production of tumor necrosis factor TNFalpha, interleukin (IL)-10 and IL-12p40 were determined. TB patients presented higher percentage of CD14+ cells but lower percentage of CD14+DR+ and CD14+CD36+ cells. Expression of CD14, HLA-DR and CD36 was decreased in TB patients. Normal percentages and expression were restored during anti-TB treatment. Monocytes from TB patients underwent necrosis and apoptosis after M. tuberculosis infection, whereas monocytes from healthy controls exhibited only apoptosis. Anti-TB treatment reverted necrosis. There were no differences between the various clinical forms of TB. In vitro M. tuberculosis infection decreased expression of the membrane molecules studied. HLA-DR and CD36 inhibition correlated with induction of apoptosis. Restoration of monocyte alterations during anti-TB treatment suggests that such alterations may be caused by the high M. tuberculosis load present during active disease.     

Incorporation of HLA-DR into the envelope of human immunodeficiency virus type 1 in vivo: correlation with stage of disease and presence of opportunistic infection

Human immunodeficiency virus type 1 (HIV-1) bearing HLA-DR in its envelope was detected in plasma from all patients with chronic HIV-1 infection (n = 16) and was present at higher levels in patients with active tuberculosis coinfection (n = 6). Intriguingly, however, HLA-DR was not detectable in HIV-1 from patients during primary viremia (n = 6), suggesting the possibility of virus replication in less-activated cells.     

IFN-gamma-inducible protein 10 and pentraxin 3 plasma levels are tools for monitoring inflammation and disease activity in Mycobacterium tuberculosis infection

IFN-gamma-inducible protein 10 (IP-10/CXCL10) is a chemokine involved in delayed-type hypersensitivity and attraction of monocytes and activated T lymphocytes at inflammatory foci, whereas pentraxin 3 (PTX3) is part of the innate immune response. In the Republic of Guinea, 220 newly diagnosed, HIV-negative, pulmonary tuberculosis (TB) patients were studied together with 220 healthy household controls and 220 community controls. CXCL10 and PTX3 blood levels were assessed by ELISA at diagnosis, after 2 months and at the end of treatment. In untreated patients, both CXCL10 and PTX3 levels were higher (P < 0.0001) than in controls, although household controls had higher (P < 0.0001) CXCL10 and PTX3 levels than community controls, but lower (P < 0.0001) than those of patients. At the end of treatment, 186 cured patients showed reduction (P < 0.0001) in both CXCL10 and PTX3 levels. In 34 patients with treatment failure, both CXCL10 and PTX3 levels increased further. In five previously healthy households who developed TB during the follow-up and in two patients who relapsed after treatment, a remarkable increase in both CXCL10 and PTX3 plasma levels was observed. Active TB is associated with increased CXCL10 and PTX3 levels in the plasma. Although not specific for TB, measurement of these proteins may help the monitoring of disease activity and efficacy of therapy.