Evaluación de citoquinas, enzimas y anticuerpos como biomarcadores útiles para el diagnóstico diferencial de pleuresías infecciosas y malignas

El diagnostico de la Pleuresía tuberculosa plantea aún dificultades para la clínica dado esta afección comparte muchas características con otros exudados pleurales de origen maligno e infeccioso. En el presente estudio se describe el desarrollo y puesta a punto de una serie de metodologías de detección de biomarcadores a fin de evaluar su posible valor en la clasificación diferencial de exudados pleurales de distinto origen. Nuestros resultados indican que los ensayos basados en detección de Anticuerpos específicos como así también la determinación de actividad peroxidasa en líquido pleural (LP) no presentan características que justifiquen su consideración como candidatos útiles. Por otro lado, tanto el interferón gamma (IFN-γ) endógeno presente en la efusión pleural como la producción de IFN-γ frente a la estimulación ex vivo con Mycobacterium tuberculosis (Mtb), son predictores promisorios de pleuresía de origen tuberculoso (TB).Fil: Schierloh, Luis Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Musella, Rosa María. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Gaona Colmán, Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Caece. Departamento de Administracion y Ciencias Sociales.; ArgentinaFil: de Casado, Graciela C.. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Tisioneumonología "raúl F. Vaccarezza".; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentin

Tolerance to lipopolysaccharide promotes an enhanced neutrophil extracellular traps formation leading to a more efficient bacterial clearance in mice

Tolerance to lipopolysaccharide (LPS) constitutes a stress adaptation, in which a primary contact with LPS results in a minimal response when a second exposure with the same stimulus occurs. However, active important defence mechanisms are mounted during the tolerant state. Our aim was to assess the contribution of polymorphonuclear neutrophils (PMN) in the clearance of bacterial infection in a mouse model of tolerance to LPS. After tolerance was developed, we investigated in vivo different mechanisms of bacterial clearance. The elimination of a locally induced polymicrobial challenge was more efficient in tolerant mice both in the presence or absence of local macrophages. This was related to a higher number of PMN migrating to the infectious site as a result of an increased number of PMN from the marginal pool with higher chemotactic capacity, not because of differences in their phagocytic activity or reactive species production. In vivo, neutrophils extracellular trap (NET) destruction by nuclease treatment abolished the observed increased clearance in tolerant but not in control mice. In line with this finding, in vitro NETs formation was higher in PMN from tolerant animals. These results indicate that the higher chemotactic response from an increased PMN marginal pool and the NETs enhanced forming capacity are the main mechanisms mediating bacterial clearance in tolerant mice. To sum up, far from being a lack of response, tolerance to LPS causes PMN priming effects which favour distant and local anti-infectious responses.Fil: Landoni, Verónica Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Chiarella, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Martire Greco, Daiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Schierloh, Luis Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: van Rooijen, N.. University Of Amsterdam. Department of Molecular Biology; Países BajosFil: Rearte, María Bárbara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Palermo, Marina Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Isturiz, Martín Amadeo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Fernández, Gabriela Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentin

Mycobacterium tuberculosis impairs dendritic cell response by altering CD1b, DC-SIGN and MR profile

During a chronic infection such as tuberculosis, the pool of tissue dendritic cells (DC) must be renewed by recruitment of both circulating DC progenitors and monocytes (Mo). However, the microenvironment of the inflammatory site affects Mo differentiation. As DC are critical for initiating a Mycobacterium tuberculosis-specific T-cell response, we argue that interference of M. tuberculosis with a correct DC generation would signify a mechanism of immune evasion. In this study, we showed thatearly interaction of c-irradiated M. tuberculosis with Mo subverts DC differentiation in vitro. We found that irradiated M. tuberculosis effect involves (1) the loss of a significant fraction of monocyte population and (2) an altered differentiation process of the surviving monocyte subpopulation. Moreover, in the absence of irradiated M. tuberculosis, DC consist in a major DC-specific intercellular adhesion molecule 3-grabbing non-integrin receptor (DC-SIGNhigh)/CD86low and minor DCSIGNlow/CD86high subpopulations, whereas in the presence of bacteria, there is an enrichment of DC-SIGNlow/CD86high population. Besides, this population enlarged by irradiated M. tuberculosis, which is characterized by a reduced CD1b expression, correlates with a reduced induction of specific T-lymphocyte proliferation. The loss of CD1molecules partially involves toll-like receptors (TLR-2)/p38 MAPK activation. Finally, several features of Mo, which have been differentiated into DC in the presence of irradiated M. tuberculosis, resemble the features of DC obtained from patients with active tuberculosis. In conclusion, we suggest that M. tuberculosis escapes from acquired immune response in tuberculosis may be caused by an altered differentiation into DC leading to a poor M. tuberculosis-specific T-cell response.Fil: Balboa, Luciana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Romero, María Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Yokobori, Noemí. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Schierloh, Pablo. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; ArgentinaFil: Geffner, Laura Judith. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Basile, Juan Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Musella, Rosa María. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Abbate, Eduardo. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: de la Barrera, Silvia Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Sasiain, María del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Alemán, Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentin

Delayed viral clearance despite high number of activated T cells during the acute phase in Argentinean patients with hantavirus pulmonary syndrome

Background: The hallmarks of HPS are increase of vascular permeability and endothelial dysfunction. Although an exacerbated immune response is thought to be implicated in pathogenesis, clear evidence is still elusive. As orthohantaviruses are not cytopathic CD8+ T cells are believed to be the central players involved in pathogenesis. Methods: Serum and blood samples from Argentinean HPS patients were collected from 2014 to 2019. Routine white blood cell analyses, quantification and characterization of T-cell phenotypic profile, viral load, neutralizing antibody response and quantification of inflammatory mediators were performed. Findings: High numbers of activated CD4+ and CD8+ T cells were found in all HPS cases independently of disease severity. We found increased levels of some proinflammatory mediators during the acute phase of illness. Nonetheless, viral RNA remained high, showing a delay in clearance from blood up to late convalescence, when titers of neutralizing antibodies reached a high level. Interpretation: The high activated phenotypic profile of T cells seems to be unable to resolve infection during the acute and early convalescent phases, and it was not associated with the severity of the disease. Thus, at least part of the activated T cells could be induced by the dysregulated inflammatory response in an unspecific manner. Viral clearance seems to have been more related to high titers of neutralizing antibodies than to the T-cell response. Funding: This work was supported mainly by the Administración Nacional de Laboratorios e Institutos de Salud (ANLIS) “Dr. Carlos Malbrán”. Further details of fundings sources is included in the appendix.Fil: Iglesias, Ayelén Aluminé. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; ArgentinaFil: Periolo, Natalia. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bellomo, Carla María. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; ArgentinaFil: Lewis, Lorena Cecilia. Provincia del Chubut. Servicio de Salud Mental. Hospital Zonal de Esquel; ArgentinaFil: Olivera, Camila Paula. Provincia del Chubut. Servicio de Salud Mental. Hospital Zonal de Esquel; ArgentinaFil: Rosario Anselmo, Constanza. Provincia del Chubut. Servicio de Salud Mental. Hospital Zonal de Esquel; ArgentinaFil: García, Marina. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Coelho, Rocío María. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; ArgentinaFil: Alonso, Daniel Oscar. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; ArgentinaFil: Dighero Kemp, Bonnie. National Institute Of Allergy And Infectious Diseases; Estados UnidosFil: Sharma, Heema. National Institute Of Allergy And Infectious Diseases; Estados UnidosFil: Kuhn, Jens H.. National Institute Of Allergy And Infectious Diseases; Estados UnidosFil: Di Paola, Nicholas. Center For Genome Sciences, U.s. Army Medical Research; Estados UnidosFil: Sanchez Lockhart, Mariano. Center For Genome Sciences, U.s. Army Medical Research; Estados UnidosFil: Palacios, Gustavo. Center For Genome Sciences, U.s. Army Medical Research; Estados UnidosFil: Schierloh, Luis Pablo. Universidad Nacional de Entre Ríos. Instituto de Investigación y Desarrollo en Bioingeniería y Bioinformática - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Investigación y Desarrollo en Bioingeniería y Bioinformática; ArgentinaFil: Martinez, Valeria Paula. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; Argentin

Revisiting Molossus (Mammalia: Chiroptera: Molossidae) diversity: Exploring southern limits and revealing a novel species in Argentina

Abstract Understanding species diversity and delineating their boundaries are crucial for effective management and conservation efforts. In the case of bats, species identification holds particular importance from an epidemiological standpoint. The genus Molossus (Chiroptera: Molossidae) encompasses 15 species distributed across the Neotropics, ranging from the southeastern United States to Argentina. This genus exhibits two contrasting patterns of variation: some species are cryptic, while others are morphologically distinct yet genetically similar. This study explores the diversity of Molossus in Argentina through a molecular phylogenetic approach. We analyzed sequences from three molecular markers (cyt b, COI, and FGB) along with morphology data obtained from a sample of 64 individuals. Uni- and multivariate analyses of external and cranial measurements were conducted, alongside comparisons of external and cranial characteristics among species. Based on molecular and morphological differences, we describe a new species within the Molossus genus. This newly discovered species exhibits a broad distribution spanning the Paraná River basin across three distinct ecoregions. It is noteworthy that this species is pseudo-cryptic with respect to similar-sized species such as M. molossus and M. melini. Additionally, it is important to mention that all species in Argentina have overlapping distribution ranges. In summary, this study provides valuable insights into the diversity and distribution of Molossus bats in Argentina, employing molecular and morphological analyses. The discovery of a new species underscores the ongoing importance of comprehensive research efforts in understanding and conserving bat populations in the Neotropics

Patients with Multidrug-Resistant Tuberculosis display impaired Th1 responses and enhanced regulatory T-Cell levels in response to an outbreak of Multidrug-Resistant Mycobacterium tuberculosis M and Ra Strains

Fil: Geffner, Laura. Academia Nacional de Medicina. Instituto de Investigaciones Hematológicas Mariano R. Castex; Argentina.Fil: Yokobori, Noemi. Academia Nacional de Medicina. Instituto de Investigaciones Hematológicas Mariano R. Castex; Argentina.Fil: Basile, Juan. Academia Nacional de Medicina. Instituto de Investigaciones Hematológicas Mariano R. Castex; Argentina.Fil: Schierloh, Pablo. Academia Nacional de Medicina. Instituto de Investigaciones Hematológicas Mariano R. Castex; Argentina.Fil: Balboa, Luciana. Academia Nacional de Medicina. Instituto de Investigaciones Hematológicas Mariano R. Castex; Argentina.Fil: Mercedes Romero, María. Academia Nacional de Medicina. Instituto de Investigaciones Hematológicas Mariano R. Castex; Argentina.Fil: Ritacco, Viviana. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Vescovo, Marisa. Hospital Muñiz. Instituto de Tisioneumonología; Argentina.Fil: Gonzalez Montaner, Pablo. Hospital Muñiz. Instituto de Tisioneumonología; Argentina.Fil: López, Beatriz. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Barrera, Lucía. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Alemán, Mercedes. Academia Nacional de Medicina. Instituto de Investigaciones Hematológicas Mariano R. Castex; Argentina.Fil: Sasiain, María C. Academia Nacional de Medicina. Instituto de Investigaciones Hematológicas Mariano R. Castex; Argentina.Fil: de la Barrera, Silvia. Academia Nacional de Medicina. Instituto de Investigaciones Hematológicas Mariano R. Castex; Argentina.Fil: Abbate, Eduardo. Hospital Muñiz. Instituto de Tisioneumonología; Argentina.In Argentina, multidrug-resistant tuberculosis (MDR-TB) outbreaks emerged among hospitalized patients with AIDS in the early 1990s and thereafter disseminated to the immunocompetent community. Epidemiological, bacteriological, and genotyping data allowed the identification of certain MDR Mycobacterium tuberculosis outbreak strains, such as the so-called strain M of the Haarlem lineage and strain Ra of the Latin America and Mediterranean lineage. In the current study, we evaluated the immune responses induced by strains M and Ra in peripheral blood mononuclear cells from patients with active MDR-TB or fully drug-susceptible tuberculosis (S-TB) and in purified protein derivative-positive healthy controls (group N). Our results demonstrated that strain M was a weaker gamma interferon (IFN-gamma) inducer than H37Rv for group N. Strain M induced the highest interleukin-4 expression in CD4(+) and CD8(+) T cells from MDR-and S-TB patients, along with the lowest cytotoxic T-lymphocyte (CTL) activity in patients and controls. Hence, impairment of CTL activity is a hallmark of strain M and could be an evasion mechanism employed by this strain to avoid the killing of macrophages by M-specific CTL effectors. In addition, MDR-TB patients had an increased proportion of circulating regulatory T cells (Treg cells), and these cells were further expanded upon in vitro M. tuberculosis stimulation. Experimental Treg cell depletion increased IFN-gamma expression and CTL activity in TB patients, with M-and Ra-induced CTL responses remaining low in MDR-TB patients. Altogether, these results suggest that immunity to MDR strains might depend upon a balance between the individual host response and the ability of different M. tuberculosis genotypes to drive Th1 or Th2 profiles

Shiga Toxin 1 Induces on Lipopolysaccharide-Treated Astrocytes the Release of Tumor Necrosis Factor-alpha that Alter Brain-Like Endothelium Integrity

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

CD4+ T Lymphocytes with follicular helper phenotype (T FH) in patients with SH2D1A deficiency (XLP)

Peripheral blood mononuclear cells with T FH phenotype from two asymptomatic XLP patients were studied. Normal/high numbers of CXCR5+, CD4+ T cells coexpressing PD-1 were demonstrated. Peripheral blood mononuclear cells (PBMC) from these patients responded to sub-optimal PHA/IL-2 stimulation upregulating ICOS and CD40L and increasing intracellular expression of IL-10, IL-21 and IL-4 by CD4+ T FH cells. However when compared to N, the time profile of activation and cytokine synthesis was different in XLP and N. While ICOS and CD40L expression in N decreased after 6-8days, it continued to increase or was maintained in XLP cultures. Intracellular IL-10, IL-21 and IL-4 reached higher values in XLP than N after 8days. Rather than the absence of T FH cells or their intrinsic inability to respond to stimuli, differences in the time profile of their response could contribute to impair their role as helpers of B lymphocytes. © 2011 Elsevier Inc.Fil: Coraglia, Ana Carina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Felippo, Marta Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Schierloh, Luis Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Malbrán, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: González Bracco, María de las Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentin

Human pleural B-cells regulate IFN-γ production by local T-cells and NK cells in a Mycobacterium tuberculosis-induced delayed hypersensitivity reaction

DTH (delayed type hypersensitivity) reactions are secondary cellular immune responses that appear 24–72 h after antigen exposure. Tuberculous pleurisy is a common manifestation of extrapulmonary TB (tuberculosis) and is considered a human model of Th1-mediated DTH. In order to identify functional cross-talk among cellular populations sited in this inflammatory microenvironment, we analysed phenotypic and functional features of human B-cells isolated from the PF (pleural fluid) of TB patients. Freshly isolated PF-B-cells displayed a lower expression of CD20, CD1d and HLA-DR, and a higher expression of CD95, CD38, CD25, CXCR3 (CXC chemokine receptor 3) and CXCR4 (CXC chemokine receptor 4) than their PB (peripheral blood) counterparts, suggesting a non-classical in situ activation. Although memory PF-T-cell frequencies were increased, the frequencies of memory PF-B-cells were not. We demonstrated that, upon stimulation with γ-irradiated M. tuberculosis, mycobacterially secreted proteins or a lectin mitogen, PF-B-cells had a strong activation and produced IL-10 by a mechanism that was dependent on bystander activation of CD19− PF cells. Besides, within PF cells, B-cells diminished in vitro M. tuberculosis-induced IFN (interferon)-γ production by T-cells and NK (natural killer) cells in an IL-10-dependent manner. Finally, we found that the lower the frequency of B-cells, the higher the ratio of IFN-γ/IL-10 within PF. Thus our results suggest that B-cells can regulate a human DTH reaction induced by M. tuberculosis.Fil: Schierloh, Luis Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Landoni, Verónica Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Balboa, Luciana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Musella, Rosa María. Ciudad Autónoma de Buenos Aires. Hospital F. J. Muñiz; ArgentinaFil: Castagnino, Jorge. Ciudad Autónoma de Buenos Aires. Hospital F. J. Muñiz; ArgentinaFil: Moraña, Eduardo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Tisioneumonologia "Dr. R. F Vaccarezza"; ArgentinaFil: de Casado, Graciela C.. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Tisioneumonologia "Dr. R. F Vaccarezza"; ArgentinaFil: Palmero, Domingo. Ciudad Autónoma de Buenos Aires. Hospital F. J. Muñiz; ArgentinaFil: Sasiain, María del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentin