Pablo Schierloh
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Publications (20) View all

  • Article: Two genetically-related multidrug-resistant Mycobacterium tuberculosis strains induce divergent outcomes of infection in two human macrophage models.
    Noemí Yokobori, Beatriz López, Laura Geffner, Carmen Sabio Y García, Pablo Schierloh, Lucía Barrera, Silvia de la Barrera, Shunsuke Sakai, Ikuo Kawamura, Masao Mitsuyama, Viviana Ritacco, María Del Carmen Sasiain
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    ABSTRACT: Mycobacterium tuberculosis has a considerable degree of genetic variability resulting in different epidemiology and disease outcomes. We evaluated the pathogen-host cell interaction of two genetically closely-related multidrug-resistant M. tuberculosis strains of the Haarlem family, namely the strain M, responsible for an extensive multidrug-resistant tuberculosis outbreak, and its kin strain 410 which caused a single case in two decades. Intracellular growth and cytokine responses were evaluated in human monocyte-derived macrophages and dU937 macrophage-like cells. In monocyte-derived macrophages, strain M grew more slowly and induced lower levels of TNF-α and IL-10 than 410, contrasting with previous studies with other strains, where a direct correlation was observed between increased intracellular growth and epidemiological success. On the other hand, in dU937 cells, no difference in growth was observed between both strains, and strain M induced significantly higher TNF-α levels than strain 410. We found that both cell models differed critically in the expression of receptors for M. tuberculosis entry, which might explain the different infection outcomes. Our results in monocyte-derived macrophages suggest that strain M relies on a modest replication rate and cytokine induction, keeping a state of quiescence and remaining rather unnoticed by the host. Collectively, our results underscore the impact of M. tuberculosis intra-species variations on the outcome of host cell infection and show that results can differ depending on the in vitro infection model.
    Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases 01/2013; · 3.22 Impact Factor
  • Article: Impaired dendritic cell differentiation of CD16-positive monocytes in tuberculosis: role of p38 MAP kinase.
    Luciana Balboa, María M Romero, Evangelina Laborde, Carmen A Sabio Y García, Juan I Basile, Pablo Schierloh, Noemí Yokobori, Rosa M Musella, Jorge Castagnino, Silvia de la Barrera, María C Sasiain, Mercedes Alemán
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    ABSTRACT: Tuberculosis (TB) is one of the world's most pernicious diseases mainly due to immune evasion strategies displayed by its causative agent Mycobacterium tuberculosis (Mtb). Blood monocytes (Mos) represent an important source of DCs during chronic infections; consequently, the alteration of their differentiation constitutes an escape mechanism leading to mycobacterial persistence. We evaluated whether the CD16(+) /CD16(-) Mo ratio could be associated with the impaired Mo differentiation into DCs found in TB patients. The phenotype and ability to stimulate Mtb-specific memory clones DCs from isolated Mo subsets were assessed. We found that CD16(-) Mos differentiated into CD1a(+) DC-SIGN(high) cells achieving an efficient recall response, while CD16(+) Mos differentiated into a CD1a(-) DC-SIGN(low) population characterized by a poor mycobacterial Ag-presenting capacity. The high and sustained phosphorylated p38 expression observed in CD16(+) Mos was involved in the altered DC profile given that its blockage restored DC phenotype and its activation impaired CD16(-) Mo differentiation. Furthermore, depletion of CD16(+) Mos indeed improved the differentiation of Mos from TB patients towards CD1a(+) DC-SIGN(high) DCs. Therefore, Mos from TB patients are less prone to differentiate into DCs due to their increased proportion of CD16(+) Mos, suggesting that during Mtb infection Mo subsets may have different fates after entering the lungs.
    European Journal of Immunology 11/2012; · 5.10 Impact Factor
  • Article: Differential induction of macrophage cell death by antigens of a clustered and a non-clustered multidrug-resistant Mycobacterium tuberculosis strain from Haarlem family.
    Noemí Yokobori, Carmen A Sabio Y García, Laura Geffner, Pablo Schierloh, Beatriz López, Viviana Ritacco, Lucía Barrera, Silvia de la Barrera, María Del Carmen Saisiain
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    ABSTRACT: Some multidrug-resistant (MDR) Mycobacterium tuberculosis (Mtb) genotypes are the cause of large outbreaks, including strain M identified in Argentina. In contrast, its kin strain 410 has only caused a single case to date. Cell wall antigens from Mtb were associated with the modulation of macrophage (MΦ) cell death, and the ability to inhibit of MΦ apoptosis is considered a virulence mechanism. In this study, the ability these two clinical isolates with divergent epidemiology to induce MΦ cell death was evaluated using whole inactivated bacteria. We showed that gamma-irradiated (I-) strains induced MΦ necrosis, the strongest inducer being I-410. Cell death biased towards apoptosis with the heat-killed (hk) strains, both hk-MDR strains being poorer inducers of MΦ apoptosis than was H37Rv. These effects were partly due to their ability to induce anti-apoptotic mechanisms which were not related to the lack of tumor necrosis factor alpha induction or a compensatory effect of interleukin-10. The most noticeable difference between strain M and strain 410 was the ability shown by hk-M to interfere with apoptosis induced by hk-H37Rv. Thus, heat-stable and heat-labile antigens from these epidemiologically divergent Mtb strains differ in their ability to manipulate MΦ death.
    FEMS Immunology & Medical Microbiology 08/2012; · 2.44 Impact Factor
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    Article: Shiga toxin 1 induces on lipopolysaccharide-treated astrocytes the release of tumor necrosis factor-alpha that alter brain-like endothelium integrity.
    Verónica I Landoni, Pablo Schierloh, Marcelo de Campos Nebel, Gabriela C Fernández, Cecilia Calatayud, María J Lapponi, Martín A Isturiz
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    ABSTRACT: The hemolytic uremic syndrome (HUS) is characterized by hemolytic anemia, thrombocytopenia and renal dysfunction. The typical form of HUS is generally associated with infections by Gram-negative Shiga toxin (Stx)-producing Escherichia coli (STEC). Endothelial dysfunction induced by Stx is central, but bacterial lipopolysaccharide (LPS) and neutrophils (PMN) contribute to the pathophysiology. Although renal failure is characteristic of this syndrome, neurological complications occur in severe cases and is usually associated with death. Impaired blood-brain barrier (BBB) is associated with damage to cerebral endothelial cells (ECs) that comprise the BBB. Astrocytes (ASTs) are inflammatory cells in the brain and determine the BBB function. ASTs are in close proximity to ECs, hence the study of the effects of Stx1 and LPS on ASTs, and the influence of their response on ECs is essential. We have previously demonstrated that Stx1 and LPS induced activation of rat ASTs and the release of inflammatory factors such as TNF-α, nitric oxide and chemokines. Here, we demonstrate that rat ASTs-derived factors alter permeability of ECs with brain properties (HUVECd); suggesting that functional properties of BBB could also be affected. Additionally, these factors activate HUVECd and render them into a proagregant state promoting PMN and platelets adhesion. Moreover, these effects were dependent on ASTs secreted-TNF-α. Stx1 and LPS-induced ASTs response could influence brain ECs integrity and BBB function once Stx and factors associated to the STEC infection reach the brain parenchyma and therefore contribute to the development of the neuropathology observed in HUS.
    PLoS Pathogens 03/2012; 8(3):e1002632. · 9.13 Impact Factor
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    Chapter: Role of NK Cells in Tuberculous Pleurisy as Innate Promoters of Local Type 1 Immunity with Potential Application on Differential Diagnosis
    Pablo Schierloh, Silvia De La Barrera, Maria Sasiain
    02/2012; , ISBN: 978-953-307-942-4
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