Pasteur Institute in Antananarivo

Antananarivo, Madagascar

Pasteur Institute in Antananarivo

Antananarivo, Madagascar
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Ratovoson R.,Pasteur Institute in Antananarivo | Raharimanga V.,Pasteur Institute in Antananarivo | Rakotosamimanana N.,Pasteur Institute in Antananarivo | Ravaloson B.,Tuberculosis Treatment Center | And 7 more authors.
PLoS ONE | Year: 2014

Background: Tuberculosis continues to cause unacceptably high levels of disease and death worldwide. Active preventive strategies are required to improve tuberculosis control and to increase the number of cases treated in developing countries. The aim of this study was to evaluate the utility of the tuberculin skin test (TST) in first-year schoolchildren as a means of increasing the number of tuberculosis cases detected through the screening of close contacts. Methods: All members of the households of 90 schoolchildren assigned to three groups on the basis of TST category (# 5 mm, [5-15)mm, 15 mm) were screened for sputum smear-positive pulmonary tuberculosis. The percentage detection of tuberculosis in close contacts was compared between TST categories. Results: We identified 433 close contacts of the 90 schoolchildren, who were then evaluated for tuberculosis. We identified 11 cases of pulmonary tuberculosis among the close contacts (7 already on treatment and 4 previously undiagnosed): 0 in TST category #5 mm, 3 in TST category [5-15) mm and 8 in TST category 15 mm). This approach increased the detection of tuberculosis cases by a factor of 1.6 in first-year schoolchildren of the TST 5 mm group. Conclusion: TST in first-year schoolchildren is a potentially effective method for improving the detection of tuberculosis in close contacts. Copyright: © 2014 Reekie et al.


Lastrucci C.,CNRS Institute of Pharmacology and Structural Biology | Lastrucci C.,University Paul Sabatier | Benard A.,CNRS Institute of Pharmacology and Structural Biology | Benard A.,University Paul Sabatier | And 23 more authors.
Cell Research | Year: 2015

The human CD14 + monocyte compartment is composed by two subsets based on CD16 expression. We previously reported that this compartment is perturbed in tuberculosis (TB) patients, as reflected by the expansion of CD16 + monocytes along with disease severity. Whether this unbalance is beneficial or detrimental to host defense remains to be elucidated. Here in the context of active TB, we demonstrate that human monocytes are predisposed to differentiate towards an anti-inflammatory (M2-like) macrophage activation program characterized by the CD16 + CD163 + MerTK + pSTAT3 + phenotype and functional properties such as enhanced protease-dependent motility, pathogen permissivity and immunomodulation. This process is dependent on STAT3 activation, and loss-of-function experiments point towards a detrimental role in host defense against TB. Importantly, we provide a critical correlation between the abundance of the CD16 + CD163 + MerTK + pSTAT3 + cells and the progression of the disease either at the local level in a non-human primate tuberculous granuloma context, or at the systemic level through the detection of the soluble form of CD163 in human sera. Collectively, this study argues for the pathogenic role of the CD16 + CD163 + MerTK + pSTAT3 + monocyte-to-macrophage differentiation program and its potential as a target for TB therapy, and promotes the detection of circulating CD163 as a potential biomarker for disease progression and monitoring of treatment efficacy. © 2015 IBCB, SIBS, CAS.


Troegeler A.,CNRS Institute of Pharmacology and Structural Biology | Troegeler A.,University Paul Sabatier | Lugo-Villarino G.,CNRS Institute of Pharmacology and Structural Biology | Lugo-Villarino G.,University Paul Sabatier | And 18 more authors.
PLoS ONE | Year: 2015

Understanding the molecular components of immune recognition of the tuberculosis (TB) bacillus, Mycobacterium tuberculosis, can help designing novel strategies to combat TB. Here, we identify collectin CL-LK as a novel soluble C-type lectin able to bind M. tuberculosis, and characterize mycobacterial mannose-capped lipoarabinomannan as a primary ligand for CL-LK. Mice deficient in CL-K1, one of the CL-LK subunits, do not display altered susceptibility to M. tuberculosis. However, we found that the amount of CL-LK in the serum of patients with active TB is reduced, compared to that in controls, and correlates inversely to the magnitude of the immune response to the pathogen. These findings indicate that CL-LK might be of interest for future diagnostic and treatment monitoring purposes. © 2015 Troegeler et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


PubMed | CNRS Institute of Pharmacology and Structural Biology, Biomedical Primate Research Center, Pasteur Institute in Antananarivo, Hospital Of Infecciosas Dr Fj Muniz and 2 more.
Type: Journal Article | Journal: Cell research | Year: 2015

The human CD14(+) monocyte compartment is composed by two subsets based on CD16 expression. We previously reported that this compartment is perturbed in tuberculosis (TB) patients, as reflected by the expansion of CD16(+) monocytes along with disease severity. Whether this unbalance is beneficial or detrimental to host defense remains to be elucidated. Here in the context of active TB, we demonstrate that human monocytes are predisposed to differentiate towards an anti-inflammatory (M2-like) macrophage activation program characterized by the CD16(+)CD163(+)MerTK(+)pSTAT3(+) phenotype and functional properties such as enhanced protease-dependent motility, pathogen permissivity and immunomodulation. This process is dependent on STAT3 activation, and loss-of-function experiments point towards a detrimental role in host defense against TB. Importantly, we provide a critical correlation between the abundance of the CD16(+)CD163(+)MerTK(+)pSTAT3(+) cells and the progression of the disease either at the local level in a non-human primate tuberculous granuloma context, or at the systemic level through the detection of the soluble form of CD163 in human sera. Collectively, this study argues for the pathogenic role of the CD16(+)CD163(+)MerTK(+)pSTAT3(+) monocyte-to-macrophage differentiation program and its potential as a target for TB therapy, and promotes the detection of circulating CD163 as a potential biomarker for disease progression and monitoring of treatment efficacy.

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