Please use this identifier to cite or link to this item: http://sgc.anlis.gob.ar/handle/123456789/407
Title: 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
Authors: Geffner, Laura 
Yokobori, Noemi 
Basile, Juan 
Schierloh, Pablo 
Balboa, Luciana 
Mercedes Romero, María 
Ritacco, Viviana 
Vescovo, Marisa 
Gonzalez Montaner, Pablo 
López, Beatriz 
Barrera, Lucía 
Alemán, Mercedes 
Abbate, Eduardo 
Sasiain, María C. 
de la Barrera, Silvia 
Keywords: Tuberculosis;Mycobacterium tuberculosis;Resistencia a Medicamentos
Issue Date: 2009
Description: 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.
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.
URI: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2772532/pdf/0224-09.pdf
http://sgc.anlis.gob.ar/handle/123456789/407
ISSN: 0019-9567
Rights: 2010-05-31
info:eu-repo/semantics/embargoedAccess
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