Artículo
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
Geffner, Laura Judith
; Yokobori, Noemí
; Basile, Juan Ignacio
; Schierloh, Luis Pablo
; Balboa, Luciana
; Romero, María Mercedes
; Ritacco, Gloria Viviana
; Vescovo, Marisa; Montaner, Pablo González; Lopez, Beatriz; Barrera, Lucía; Alemán, Mercedes
; Abatte, Eduardo; Sasiain, María del Carmen
; de la Barrera, Silvia Susana
Fecha de publicación:
11/2009
Editorial:
American Society for Microbiology
Revista:
Infection and Immunity
ISSN:
0019-9567
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
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 strainMof 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-γ) 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-γ 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. Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Palabras clave:
Mycobacterium Tuberculosis
,
Mdr Strains
,
Th1 Response
,
T Regulatory
,
Mdr-Tb
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Articulos de INST.DE MEDICINA EXPERIMENTAL
Articulos de INST.DE MEDICINA EXPERIMENTAL
Citación
Geffner, Laura Judith; Yokobori, Noemí; Basile, Juan Ignacio; Schierloh, Luis Pablo; Balboa, Luciana; et al.; 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; American Society for Microbiology; Infection and Immunity; 77; 11; 11-2009; 5025-5034
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